Pyridine compounds which are useful as leukotriene b4 antagonist

ABSTRACT

Leukotriene B 4  antagonists of the formula: ##STR1## wherein each symbol is as defined in the specification, processes for producing them, and pharmaceutical compositions containing them. The compounds of the present invention are very useful as the drugs for the treatment of allergic and inflammatory diseases.

BACKGROUND OF THE INVENTION

1. Technical Field

The present invention relates to compounds effective as leukotriene B₄antagonists.

More particularly, this invention relates to leukotriene B₄ antagonists,to processes for producing them and to pharmaceutical compositionscontaining at least one of those leukotriene B₄ antagonists, which haveexcellent anti-leukotriene B₄ activity and are useful as ananti-allergic agent or an anti-inflammatory agent.

2. Prior Art

In 1979 B. Sammuelsson reported the isolation and biological effects ofleukotrienes (B. Sammuelsson et al. (1980): Advances in Prostaglandinand Thromboxane Research, Vol. 6, edited by B. Sammuelsson, R. Ramwell,and R. Paaletti, P. I. Raven Press, New York).

Since then, a tremendous amount of research in the synthetic organicchemistry and pharmacology of leukotriene A₄, B₄, C₄, D₄, etc. has beenperformed.

Leukotrienes induce an increase in capillary permeability and causesmooth muscle contraction. Leukotriene B₄, one of leukotrienes which isshown below, has different pharmacological properties from the others.It is chemotactic for macrophages and neutrophils at concentrations of˜1 ng/ml (greater than any other known lipid chemotactic factor). It isdetected in the synovia of patients with rheumatoid arthritis or goutyarthritis, and in the sputum of obstructive airways diseases whichsuggest that it is a primary mediator of inflammatory and allergicstates. ##STR2##

In recent research some compounds having an antagonism on LTB₄ have beenreported. For example, ##STR3##

SUMMARY OF THE INVENTION

In accordance with the present invention, leukotriene B₄ antagonists ofthe following general formula [I] and their non-toxic pharmaceuticallyacceptable salts are provided, which have potent anti-leukotriene B₄activity which include suppression of chemotaxis, degranulation and O₂-production of leukocytes, and modulation of lymphocytes activity, etc.This action may render these compounds very useful as the drugs for thetreatment of inflammatory states or immunological disorders such asallergy, rheumatoid arthritis, and inflammatory bowel disease.

DISCLOSURE OF THE INVENTION

The novel leukotriene B₄ antagonists provided by the present inventionare those represented by the formula [I]: ##STR4## wherein A is a C₁ -C₅alkylene chain;

B is a phenylene or 6 membered heteroaromatic group which is constitutedby carbon atoms and one or two nitrogen atoms, and B may be, optionallysubstituted with one or two substituents selected from the group,consisting of a C₁ -C₅ alkyl group, a C₁ -C₅ alkoxy group, a hydroxylgroup, a carboxyl group, a nitro group and a halogen atom;

R¹ is a C₁ -C₅ alkyl group;

R² is a hydroxyl group or a C₁ -C₅ alkoxy group;

R³ and R⁴ are each independently a hydrogen atom, a C₁ -C₅ alkyl group,a C₂ -C₅ alkenyl group or a C₂ -C₅ alkynyl group;

R⁵ is a hydrogen atom, a C₁ -C₅ alkyl group or a hydroxy C₁ -C₅ alkylgroup;

R⁶ is a group of the formula:

    --X--Y--Z--R.sup.6 '

wherein

X is a phenylene group or a monocyclic 5˜6 membered hetero aromaticgroup, and X is optionally substituted with one or two substituentsselected from the group consisting of a C₁ -C₅ alkyl group, a hydroxylgroup, a carboxyl group, a nitro group and a halogen atom;

Y is a single bond or an oxygen atom;

Z is a single bond or a C₁ -C₅ alkylene chain;

provided that when Y is an oxygen atom,

X is a phenylene group and Z is a C₁ -C₅ alkylene chain;

R⁶ ' is a COOR⁷ group,

a CONR⁸ R⁹ group,

a CONHCHR²⁰ (CH₂)_(n) COOR⁷ group,

a CONHCHR²⁰ (CH₂)_(n) CONR⁸ R⁹ group,

a CONHCHR²⁰ CONHCHR²² CO₂ R⁷ group or

a sulfamoyl group,

wherein

R⁷ is a hydrogen atom, a benzyl group, a C₁ -C₅ alkyl group or an C₁ -C₅alkyl group substituted with an aminoheteroaromatic group wherein theheteroaromatic group is a monocyclic 5˜6 membered heteroaromatic group;

R⁸ and R⁹ are each independently a hydrogen atom, a C₁ -C₅ alkyl group,hydroxy C₁ -C₅ alkyl group, a hydroxyethylpyridyl group or ahydroxyethylthiazolyl group, or the group of the formula:

    --NR.sup.8 R.sup.9

represents a pyrrolidino, a piperidino or a morpholino group;

R²⁰ is a hydrogen atom, a hydroxyl group, a C₁ -C₅ alkyl group, a phenylgroup, a hydroxyphenyl group, a benzyl group, a hydroxy benzyl group ora substituted C₁ -C₅ alkyl group wherein the substituent is selectedfrom the group consisting of a hydroxyl group, a C₁ -C₅ alkoxy group, amercapto group, a methylthio group, an amino group, an indolyl group, animidazolyl group, a carboxyl group, a C₁ -C₅ alkoxycarbonyl group, acarbamoyl group and a quanidino group;

n is 0, 1, 2, 3, 4 or 5; and

R²² is a hydrogen atom, a C₁ -C₅ alkyl group or a C₁ -C₅ hydroxyalkylgroup;

or R⁶ is a CHR²⁰ (CH₂)_(n) COOR⁷ group,

a CH₂ CHR²⁰ COOR⁷ group,

a CHR²⁰ (CH₂)_(n) CONR⁸ R⁹ group,

a CH₂ CHR²⁰ CONR⁸ R⁹ group,

a CHR²⁰ (CH₂)_(n) OH group,

a CR²⁰ R²² (CH₂)_(n) OH group,

a CH₂ CHR²⁰ OH group, or

a CHR²⁰ CONHCHR²² CO₂ R⁷ group,

wherein R⁷, R⁸, R⁹, R²⁰, R²² and n are as defined above, or the group ofthe formula: ##STR5## represents an azetidino group, pyrrolidino group,a piperidino group or a homopiperidino group, which is optionallysubstituted with one to two substituents selected from the groupconsisting of a hydroxyl group, a C₁ -C₅ hydroxyalkyl group, carboxylgroup, C₁ -C₅ alkoxycarbonyl group and benzyloxycarbonyl group; orpharmaceutically acceptable salts thereof.

In the definitions as used above, the term "C₁ -C₅ alkylene" means astraight or branched chain C₁ -C₅ alkylene (e.g. methylene, ethylene,trimethylene, tetramethylene, pentamethylene, 1-methyethylene,2-ethyltrimethylene, etc.).

The term "C₁ -C₅ alkyl" means a straight or branched chain C₁ -C₅ alkyl(e.g. methyl, ethyl, n-propyl, iso-propyl, n-butyl, iso-butyl,sec-butyl, tert-butyl, n-pentyl, iso-pentyl, sec-pentyl, neo-pentyl,etc.).

The term "C₂ -C₅ alkenyl" means a straight or branched chain C₂ -C₅alkenyl (e.g. 1-methylethenyl, 1-ethylethenyl, 1-propenyl, 2-propenyl,1-methyl-1-propenyl, 2-methyl-1-propenyl, 1-methyl-2-propenyl,2-methyl-2-propenyl, 1,2-dimethyl-1-propenyl, 1-n-butenyl, 2-n-butenyl,3-n-butenyl, 1-methyl-1-butenyl, 2-methyl-1-butenyl, 3-methyl-1-butenyl,1-methyl-2-butenyl, 2-methyl-3-butenyl, 3-methyl-3-butenyl, 1-pentenyl,2-pentenyl, 3-pentenyl, 4-pentenyl, etc.).

The term "C₂ -C₅ alkynyl" means a straight or branched chain C₂ -C₅alkynyl (e.g. ethynyl, 1-propynyl, 2-propynyl, 1-methyl-2-propynyl,1-n-butynyl, 2-n-butynyl, 3-n-butynyl, 3-methyl-1-butynyl,1-methyl-2-butynyl, 2-methyl-3-butynyl, 1-pentynyl, 2-pentynyl,3-pentynyl, 4-pentynyl, etc.).

The term "C₁ -C₅ alkoxy" means alkoxy having C₁ -C₅ alkyl moiety (e.g.methoxy, ethoxy, n-propoxy, iso-propoxy, n-butoxy, iso-butoxy,sec-butoxy, tert-butoxy, n-pentoxy, iso-pentoxy, sec-pentoxy,neo-pentoxy, etc.).

The term "6 membered heteroaromatic group which is constituted by carbonatoms and one or two nitrogen atoms" includes pyridinediyl,pyrazinediyl, pyrimidinediyl, etc.

The term "monocyclic 5˜6 membered heteroaromatic group" contains, forexample, 1-3 hetero atoms which can be a nitrogen, oxygen or sulfuratom, or an oxydized nitrogen atom (N→O), and examples of the monocyclic5-6 membered heteroaromatic group are a pyridinediyl group and any oneof the group of the formula (i)-(viii): ##STR6##

The term "hydroxyphenyl group" may be a 2-hydroxyphenyl, a3-hydroxyphenyl or a 4-hydroxyphenyl group.

The term "hydroxybenzyl group" may be a 2-hydroxybenzyl, a3-hydroxybenzyl or a 4-hydroxybenzyl group.

The term "halogen" may be a chlorine, a bromine or a fluorine atom.

The term "indolyl group" may be a 2-indolyl or 3-indolyl group.

The term "imidazolyl group" may be a 4-imidazolyl group.

A basic object of the present invention is to provide novel compoundseffective as leukotriene B₄ antagonists [I] having excellentpharmacological activities.

Another object of the present invention is to provide processes forproducing those compounds [I]. A further object of the present inventionis to provide a pharmaceutical composition containing a compound of theformula [I]. These and other objects will be apparent to those skilledin the art to which the present invention pertains from the foregoingand subsequent descriptions.

The novel leukotriene B₄ antagonists [I] of the invention can beprepared by the following methods: ##STR7## wherein A, B, R¹, R², R³,R⁴, R⁵, R⁶ ', X, Y, Z and R²⁰ are as defined above, and

R¹¹ is the same as R⁶ ', but it does not means free carboxylic group;

R¹² is a group of the formula:

X-Y-Z-COOR^(7'),

X-Y-Z-CONHCHR²⁰ (CH₂)_(n) COOR^(7'),

X-Y-Z-CONHCHR²⁰ CONHCHR²² CO₂ R^(7'),

CHR²⁰ (CH₂)_(n) COOR^(7'),

CH₂ CHR²⁰ COOR^(7'), or

CHR²⁰ CONHCHR²² COOR^(7'),

wherein

X, Y, Z, R²⁰, R²² and n are as defined above, and R^(7') is the same asR⁷ but it does not mean a hydrogen atom,

R¹³ is a group of the formula:

X-Y-Z-COOH,

X-Y-Z-CONHCHR²⁰ (CH₂)_(n) COOH,

X-Y-Z-CONHCHR²⁰ CONHCHR²² CO₂ H,

CHR²⁰ (CH₂)_(n) COOH,

CH₂ CHR²⁰ COOH, or

CHR²⁰ CONHCHR²² COOH,

wherein

X, Y, Z, R²⁰, R²² and n are as defined above,

R¹⁴ is a group of the formula:

(CH₂)_(n) COOR^(7'), or

CONHCHR²² COOR^(7'),

wherein

R^(7'), R²² and n are as defined above,

R¹⁵ is a group of the formula:

COOR^(7'),

CONHCHR²⁰ (CH₂)_(n) COOR^(7'), or

CONHCHR²⁰ CONHCHR²² CO₂ R^(7'),

wherein

R^(7'), R²⁰, R²² and n are as defined above,

R¹⁶ is a group of the formula:

COOH,

CONHCHR²⁰ (CH₂)_(n) COOH, or

CONHCHR²⁰ CONHCHR²² CO₂ H,

wherein

R²⁰, R²² and n are as defined above,

R²⁶ is a group of the formula:

(CH₂)_(n) COOH, or

CONHCHR²² COOH, wherein R²² and n are as defined above.

Method A

The amide compound [IV] or [IX] can be prepared from an acid compound[II] or [VII] by reacting an amine compound [III] or [VIII] in thepresence of a condensing agent (e.g. dicyclohexylcarbodiimide,ethyldimethylaminopropylcarbodiimide hydrochloride, etc.),hydroxybenzotriazole and a tertiary amine (e.g. triethylamine,4-dimethylaminopyridine, etc.) in an inert solvent (e.g.dichloromethane, mixed solvent of dichloromethane andN,N-dimethylformamide, etc.) at a temperature in the range from 0° C. tothe boiling temperature of the solvent.

If a substituent of R²⁰ of compound [VIII] is an impediment group (e.g.mercapto, carboxyl, amino group, etc.), the compound is previouslyprotected by a protecting group (e.g. benzyl, benzyloxycarbonyl,t-butoxycarbonyl group, etc.), and after the reaction is carried out,the protecting group is eliminated. The protection and deprotection ofR²⁰ can be carried out by the conventional procedure. [Protective Groupin Organic Chemistry, Edited by J. F. W. McOmic (1973) 95-143].

Method B

The amide compound [IV] or [IX] can be obtained from an acid chloride oran acid anhydride of an acid compound [II] or [VII] by reacting with anamine compound [III] or [VIII] in the presence of a tertiary amine (e.g.triethylamine, etc.), or by reacting with a salt of an amine compound[III] or [VIII] (e.g. sodium salt, potassium salt, etc.) in the absenceof amine in an inert solvent (e.g. tetrahydrofuran, etc.) at atemperature in the range from 0° C. to a boiling temperature of thesolvent.

The transformation of an acid group to an acid chloride group can becarried out by treating the acid compound with phosphorous oxychlorideor thionyl chloride in an inert solvent (e.g. chloroform, etc.) or inthe absence of solvent at a temperature in the range of from -40° C. tothe boiling temperature of the reaction mixture.

The transformation of an acid group to an acid anhydride group can becarried out by treating the acid compound with chloroformate ester (e.g.ethyl chloroformate, etc.) in the presence of a tertiary amine (e.g.triethylamine, etc.) in an inert solvent (e.g. chloroform, etc.) at atemperature in the range of from -40° C. to the boiling temperature ofthe solvent.

If a substituent of R²⁰ of compound [VIII] is a impediment group (e.g.mercapto, carboxyl, amino group, etc.), the compound is previouslyprotected by a protecting group (e.g. benzyl group, benzyloxycarbonylgroup, t-butoxycarbonyl group, etc.), and after the reaction is carriedout, the protecting group is eliminated.

The protection and deprotection of R²⁰ can be carried out by theconventional procedure [Protective Group in Organic Chemistry, Edited byJ. F. W. McOmic (1973) 95-143].

Method C

The acid compound [VI], [X] or [XIV] can be prepared by hydrolysis ofthe ester compound [V], [IX] or [XIII] by treating with an aqueousalkali (e.g. sodium hydroxide, lithium hydroxide) in an inert solvent(e.g. tetrahydrofuran, methanol, ethanol, etc.).

Method D

The N-oxide compound [XII] can be prepared from pyridine compound [XI]by treating with an oxidizing agent (e.g. m-chloroperbenzoic acid, etc.)in an inert solvent (e.g. methylene chloride, etc.).

The amine compounds [III] and [VIII] are known compounds or easilyobtained as described in e.g. J. Goto, K. Sakane, Y. Nakai, T. Teraji,The journal of antibiotics, 37, 532 (1984), I. Csendes, B. W. Muller, W.Tosch, The journal of antibiotics, 36, 1020 (1983), M. Ohta, Yakugakuzassi, 72, 1536 (1983), JP-A-58-23697. And, the starting compounds [II],[II-1] and [II-2] can be obtained by the following method. ##STR8##(wherein A, B, R¹, R², R³ and R⁴ are as defined above, R¹⁷ is a C₁ -C₅alkyl group, R¹⁸ is a C₁ -C₅ alkyl group, R¹⁸ is a C₁ -C₅ alkyl group,Hal is a chlorine or bromine atom)

Alkylation of the compound [XV] into the compound [XVII] can beaccomplished by treating the former with the compound [XVI] in an inertsolvent (e.g. N,N-dimethylformamide, etc.) in the presence of a base(e.g. anhydrous potassium carbonate, etc.). Optionally, the compound[XVII] can be alkylated to produce the compound [XVIII] by the sameprocedure as used in the synthesis of the compound [XVII] from thecompound [XV]. And, the compound (II-1) and (II-2), respectively, can beprepared from the compound [XVII] and [XVIII] by hydrolysis (Method C).

The compound [XV] is a known compound or easily obtained as described ine.g. J. Hurst, J. Wibberley, Journal of Chemical Society, 1962, 119.

The compound [XVI] is obtained by;

(1) In the case where both Hal and B of compound [XVI] are jointed tothe same carbon atom:

the compound [XVI] is a known compound or easily obtained as describedin e.g. J. Hurst, J. Wibberley, Journal of Chemical Society, 1962, 119,etc,

(2) In the case that there are two carbon atoms between Hal and B incompound [XVI]: ##STR9## (wherein A, B and Hal are as defined above, R¹⁹is a C₁ -C₅ alkyl group (but, there is at least one hydrogen atom at theα carbon bonded to B), R²¹, R²³ are each independently a hydrogen atomor a C₁ -C₅ alkyl group, R²⁴ is a C₁ -C₅ alkyl group, and R²⁵ is a C₁-C₅ alkyl group or phenyl group)

the compound [XVI] is prepared in the following way:

first step: the carboxylic acid group of a compound [XX] is protected toyield a 4,4-dimethyl-2-oxazoline compound,

second step: the 4,4-dimethyl-2-oxazoline compound is treated with abase to deprotonate a hydrogen atom attached to a carbon atom adjacentto B group (e.g. sodium amide, n-butyl lithium, etc.),

third step: the deprotected compound is reacted with the compound of theformula [XXI] (aldehyde or ketone) to yield a hydroxy compound,

fourth step: the hydroxyl compound is alkylated by reacting with acompound of the formula R²⁴ -Hal, fifth step: the alkylated compound istreated with halogenated hydrogen (e.g. hydrogen chloride, hydrogenbromide, etc.) in the alcohol represented by R¹⁷ OH.

(3) In the case that there are 3 or more carbon atoms between Hal and Bin the compound [XVI]:

the compound [XVI] is prepared in the same way, except modifying thealkylation reaction, as described in above (2), i.e., the compound [XX]is protected and deprotonated, and then alkylated by alkylhalide [XXII].The alkylated product is treated with halogenated hydrogen (e.g.hydrogen chloride, hydrogen bromide, etc.) in the alcohol represented byR¹⁷ OH.

Specific examples of the leukotriene B₄ antagonists are as follows:

                                      TABLE 1                                     __________________________________________________________________________     ##STR10##                                                                    __________________________________________________________________________    R.sup.3                                                                          H    H    H    n-Pr H    H    H    H    H                                  R.sup.4                                                                          Me   n-Pr n-Pr H    Et   Et   Et   Et   Et                                 R.sup.5                                                                          H    H    H    H    CH.sub.3                                                                           Et   n-Pr i-Pr H                                  R.sup.6'                                                                         CONH.sub.2                                                                         CONH.sub.2                                                                         CONH.sub.2                                                                         CONH.sub.2                                                                         CONH.sub.2                                                                         CONH.sub.2                                                                         CONH.sub.2                                                                         CONH.sub.2                                                                         CONHMe                             __________________________________________________________________________

                                      TABLE 2                                     __________________________________________________________________________     ##STR11##                                                                    __________________________________________________________________________    A  CH.sub.2                                                                            CH.sub.2                                                                            CH.sub.2                                                                             CH.sub.2                                                                            CH.sub.2                                                                             (CH.sub.2).sub.2                                                                     (CH.sub.2).sub.3                                                                     (CH.sub.2).sub.4                                                                     (CH.sub.2).sub.5      R.sup.6'                                                                         CONMe.sub.2                                                                         CONHiPr                                                                              ##STR12##                                                                            ##STR13##                                                                           ##STR14##                                                                           CONH.sub.2                                                                           CONH.sub.2                                                                           CONH.sub.2                                                                           CONH.sub.2            __________________________________________________________________________

                                      TABLE 3                                     __________________________________________________________________________     ##STR15##                                                                    __________________________________________________________________________    A CHMe   CH.sub.2                                                                            CH.sub.2                                                                             CH.sub.2                                                                             CH.sub.2                                                                             CH.sub.2                                                                             CH.sub.2                                                                             CH.sub.2                                                                            CH.sub.2                 ##STR16##                                                                            ##STR17##                                                                           ##STR18##                                                                            ##STR19##                                                                            ##STR20##                                                                            ##STR21##                                                                            ##STR22##                                                                            ##STR23##                                                                           ##STR24##            Z CH.sub.2                                                                             single bond                                                                         CH.sub.2                                                                             (CH.sub.2).sub.2                                                                     (CH.sub.2).sub.3                                                                     (CH.sub.2).sub.4                                                                     (CH.sub.2) .sub.5                                                                    CH.sub.2                                                                            single                __________________________________________________________________________                                                            bond              

                                      TABLE 4                                     __________________________________________________________________________     ##STR25##                                                                    __________________________________________________________________________       ##STR26##                                                                           ##STR27##                                                                            ##STR28##                                                                            ##STR29##                                                                            ##STR30##                                                                            ##STR31##                                                                           ##STR32##                                                                            ##STR33##                                                                            ##STR34##            Z CH.sub.2                                                                            (CH.sub.2).sub.2                                                                     (CH.sub.2).sub.3                                                                     (CH.sub.2).sub.4                                                                     single bond                                                                          CH.sub.2                                                                            (CH.sub.2).sub.2                                                                     (CH.sub.2).sub.3                                                                     (CH.sub.2).sub.4      __________________________________________________________________________

                                      TABLE 5                                     __________________________________________________________________________     ##STR35##                                                                    __________________________________________________________________________       ##STR36##                                                                           ##STR37##                                                                           ##STR38##                                                                            ##STR39##                                                                            ##STR40##                                                                            ##STR41##                                                                            ##STR42##                                                                            ##STR43##                                                                            ##STR44##            X                                                                                ##STR45##                                                                           ##STR46##                                                                           ##STR47##                                                                            ##STR48##                                                                            ##STR49##                                                                            ##STR50##                                                                            ##STR51##                                                                            ##STR52##                                                                            ##STR53##            __________________________________________________________________________

                                      TABLE 6                                     __________________________________________________________________________     ##STR54##                                                                    __________________________________________________________________________       ##STR55##                                                                           ##STR56##                                                                            ##STR57##                                                                            ##STR58##                                                                            ##STR59##                                                                            ##STR60##                                                                            ##STR61##                                                                            ##STR62##                                                                            ##STR63##           X                                                                                ##STR64##                                                                           ##STR65##                                                                            ##STR66##                                                                            ##STR67##                                                                            ##STR68##                                                                            ##STR69##                                                                            ##STR70##                                                                            ##STR71##                                                                            ##STR72##           Z single bond                                                                         CH.sub.2                                                                             (CH.sub.2).sub.2                                                                     (CH.sub.2).sub.3                                                                     (CH.sub.2).sub.4                                                                     single bond                                                                          CH.sub.2                                                                             (CH.sub.2).sub.2                                                                     single               __________________________________________________________________________                                                             bond             

                                      TABLE 7                                     __________________________________________________________________________     ##STR73##                                                                    __________________________________________________________________________       ##STR74##                                                                           ##STR75##                                                                            ##STR76##                                                                            ##STR77##                                                                            ##STR78##                                                                            ##STR79##                                                                            ##STR80##                                                                            ##STR81##                                                                           ##STR82##            X                                                                                ##STR83##                                                                           ##STR84##                                                                            ##STR85##                                                                            ##STR86##                                                                            ##STR87##                                                                            ##STR88##                                                                            ##STR89##                                                                            ##STR90##                                                                           ##STR91##            Z CH.sub.2                                                                            (CH.sub.2).sub.2                                                                     (CH.sub.2).sub.3                                                                     (CH.sub.2).sub.4                                                                     single bond                                                                          CH.sub.2                                                                             (CH.sub.2).sub.2                                                                     single                                                                              CH.sub.2              __________________________________________________________________________

                                      TABLE 8                                     __________________________________________________________________________     ##STR92##                                                                    __________________________________________________________________________       ##STR93##                                                                            ##STR94##                                                                            ##STR95##                                                                            ##STR96##                                                                           ##STR97##                                                                           ##STR98##                                                                            ##STR99##                                                                            ##STR100##                                                                           ##STR101##           X                                                                                ##STR102##                                                                           ##STR103##                                                                           ##STR104##                                                                           ##STR105##                                                                          ##STR106##                                                                          ##STR107##                                                                           ##STR108##                                                                           ##STR109##                                                                           ##STR110##           Z (CH.sub.2).sub.2                                                                     (CH.sub.2).sub.3                                                                     (CH.sub.2).sub.4                                                                     CH.sub.2                                                                            single bond                                                                         (CH.sub.2).sub.2                                                                     (CH.sub.2).sub.3                                                                     (CH.sub.2).sub.4                                                                     CMe.sub.2             __________________________________________________________________________

                                      TABLE 9                                     __________________________________________________________________________     ##STR111##                                                                   __________________________________________________________________________        ##STR112##                                                                          ##STR113##                                                                          ##STR114##                                                                          ##STR115##                                                                           ##STR116##                                                                           ##STR117##                                                                           ##STR118##                                                                           ##STR119##                                                                           ##STR120##           Z  single bond                                                                         single bond                                                                         single bond                                                                         single bond                                                                          CH.sub.2                                                                             (CH.sub.2).sub.2                                                                     CH.sub.2                                                                             (CH.sub.2).sub.2                                                                     CH.sub.2              R.sup. 6'                                                                        CONH.sub.2                                                                          CONH.sub.2                                                                          SO.sub.2 NH.sub.2                                                                   SO.sub.2 NH.sub.2                                                                    CONH.sub.2                                                                           CONH.sub.2                                                                           SO.sub.2 NH.sub.2                                                                    SO.sub.                                                                              SO.sub.2 NH.sub.2     __________________________________________________________________________

                                      TABLE 10                                    __________________________________________________________________________     ##STR121##                                                                   __________________________________________________________________________    R.sup.2                                                                          OH    OH     OH     OH     OMe    OH     OH     OH    OH                   R.sup.5                                                                          H     H      H      H      H      H      Me     Et    n-Pr                     ##STR122##                                                                          ##STR123##                                                                           ##STR124##                                                                           ##STR125##                                                                           ##STR126##                                                                           ##STR127##                                                                           ##STR128##                                                                           ##STR129##                                                                          ##STR130##          Y  O     O      O      O      single bond                                                                          single bond                                                                          single bond                                                                          single                                                                              single bond          Z  CH.sub.2                                                                            (CH.sub.2).sub.2                                                                     CH.sub.2                                                                             (CH.sub.2).sub.2                                                                     CH.sub.2                                                                             CH.sub.2                                                                             CH.sub.2                                                                             CH.sub.2                                                                            CH.sub.2             R.sup. 6'                                                                        CONH.sub.2                                                                          CONH.sub.2                                                                           CONH.sub.2                                                                           CONH.sub.2                                                                           CONH.sub.2                                                                           CO.sub.2 Et                                                                          CO.sub.2 Et                                                                          CO.sub.2 Et                                                                         CO.sub.2             __________________________________________________________________________                                                             Et               

                                      TABLE 11                                    __________________________________________________________________________     ##STR131##                                                                   __________________________________________________________________________    A CH.sub.2                                                                            (CH.sub.2).sub.2                                                                     (CH.sub.2).sub.3                                                                     (CH.sub.2).sub.4                                                                     (CH.sub.2).sub.5                                                                     CHMe   CH.sub.2                                                                            CH.sub.2                                                                             CH.sub.2                 ##STR132##                                                                          ##STR133##                                                                           ##STR134##                                                                           ##STR135##                                                                           ##STR136##                                                                           ##STR137##                                                                           ##STR138##                                                                          ##STR139##                                                                           ##STR140##           R.sup.5                                                                         i-Pr  H      H      H      H      H      H     H      H                     Z CH.sub.2                                                                            CH.sub.2                                                                             CH.sub.2                                                                             CH.sub.2                                                                             CH.sub.2                                                                             CH.sub.2                                                                             CH.sub.2                                                                            (CH.sub.2).sub.2                                                                     (CH.sub.2).sub.3      __________________________________________________________________________

                                      TABLE 12                                    __________________________________________________________________________     ##STR141##                                                                   __________________________________________________________________________       ##STR142##                                                                          ##STR143##                                                                           ##STR144##                                                                           ##STR145##                                                                           ##STR146##                                                                           ##STR147##                                                                           ##STR148##                                                                           ##STR149##                                                                           ##STR150##          X                                                                                ##STR151##                                                                          ##STR152##                                                                           ##STR153##                                                                           ##STR154##                                                                           ##STR155##                                                                           ##STR156##                                                                           ##STR157##                                                                           ##STR158##                                                                           ##STR159##          Z CH.sub.2                                                                            (CH.sub.2).sub.2                                                                     (CH.sub.2).sub.3                                                                     CH.sub.2                                                                             (CH.sub.2).sub.2                                                                     (CH.sub. 2).sub.3                                                                    CH.sub.2                                                                             CH.sub.2                                                                             CH.sub.2             __________________________________________________________________________

                                      TABLE 13                                    __________________________________________________________________________     ##STR160##                                                                   __________________________________________________________________________       ##STR161##                                                                          ##STR162##                                                                          ##STR163##                                                                           ##STR164##                                                                           ##STR165##                                                                           ##STR166##                                                                           ##STR167##                                                                           ##STR168##                                                                           ##STR169##           X                                                                                ##STR170##                                                                          ##STR171##                                                                          ##STR172##                                                                           ##STR173##                                                                           ##STR174##                                                                           ##STR175##                                                                           ##STR176##                                                                           ##STR177##                                                                           ##STR178##           Z CH.sub.2                                                                            CH.sub.2                                                                            CH.sub.2                                                                             (CH.sub.2).sub.2                                                                     (CH.sub.2).sub.3                                                                     CH.sub.2                                                                             (CH.sub.2).sub.2                                                                     (CH.sub.2).sub.3                                                                     CH.sub.2              __________________________________________________________________________

                                      TABLE 14                                    __________________________________________________________________________     ##STR179##                                                                   __________________________________________________________________________       ##STR180##                                                                           ##STR181##                                                                           ##STR182##                                                                           ##STR183##                                                                           ##STR184##                                                                           ##STR185##                                                                          ##STR186##                                                                          ##STR187##                                                                           ##STR188##           X                                                                                ##STR189##                                                                           ##STR190##                                                                           ##STR191##                                                                           ##STR192##                                                                           ##STR193##                                                                           ##STR194##                                                                          ##STR195##                                                                          ##STR196##                                                                           ##STR197##           Z (CH.sub.2).sub.2                                                                     (CH.sub.2).sub.3                                                                     CH.sub.2                                                                             (CH.sub.2).sub.2                                                                     (CH.sub.2).sub.3                                                                     CH.sub.2                                                                            CH.sub.2                                                                            (CH.sub.2).sub.2                                                                     (CH.sub.2).sub.2      __________________________________________________________________________

                                      TABLE 15                                    __________________________________________________________________________     ##STR198##                                                                   __________________________________________________________________________        ##STR199##                                                                          ##STR200##                                                                          ##STR201##                                                                           ##STR202##                                                                           ##STR203##                                                                          ##STR204##                                                                           ##STR205##                                                                           ##STR206##                                                                           ##STR207##           Y  O     O     O      O      single bond                                                                         single bond                                                                          single bond                                                                          single                                                                               single bond           Z  CH.sub.2                                                                            CH.sub.2                                                                            (CH.sub.2).sub.2                                                                     (CH.sub.2).sub.2                                                                     single bond                                                                         CH.sub.2                                                                             (CH.sub.2).sub.2                                                                     (CH.sub.2).sub.3                                                                     (CH.sub.2).sub.4      R.sup. 6'                                                                        CO.sub.2 Et                                                                         CO.sub.2 Et                                                                         CO.sub.2 Et                                                                          CO.sub.2 Et                                                                          CO.sub.2 H                                                                          CO.sub.2 H                                                                           CO.sub.2 H                                                                           CO.sub.2 H                                                                           CO.sub.2 H            __________________________________________________________________________

                                      TABLE 16                                    __________________________________________________________________________     ##STR208##                                                                   __________________________________________________________________________       ##STR209##                                                                           ##STR210##                                                                          ##STR211##                                                                           ##STR212##                                                                          ##STR213##                                                                           ##STR214##                                                                           ##STR215##                                                                           ##STR216##                                                                           ##STR217##           Z (CH.sub.2).sub.5                                                                     CH.sub.2                                                                            (CH.sub.2).sub.2                                                                     CH.sub.2                                                                            (CH.sub.2).sub.2                                                                     CH.sub.2                                                                             (CH.sub.2).sub.2                                                                     CH.sub.2                                                                             (CH.sub.2).sub.2      __________________________________________________________________________

                                      TABLE 17                                    __________________________________________________________________________     ##STR218##                                                                   __________________________________________________________________________       ##STR219##                                                                          ##STR220##                                                                           ##STR221##                                                                          ##STR222##                                                                           ##STR223##                                                                           ##STR224##                                                                           ##STR225##                                                                           ##STR226##                                                                           ##STR227##           Z CH.sub.2                                                                            (CH.sub.2).sub.2                                                                     single bond                                                                         CH.sub.2                                                                             (CH.sub.2).sub.2                                                                     (CH.sub.2).sub.3                                                                     (CH.sub.2).sub.4                                                                     (CH.sub.2).sub.5                                                                     single                __________________________________________________________________________                                                            bond              

                                      TABLE 18                                    __________________________________________________________________________     ##STR228##                                                                   __________________________________________________________________________    R.sup.5                                                                         H     H      H      Me     Et     n-Pr   i-Pr   n-Bu   i-Bu                    ##STR229##                                                                          ##STR230##                                                                           ##STR231##                                                                           ##STR232##                                                                           ##STR233##                                                                           ##STR234##                                                                           ##STR235##                                                                           ##STR236##                                                                           ##STR237##          Z CH.sub.2                                                                            (CH.sub.2).sub.2                                                                     (CH.sub.2).sub.3                                                                     CH.sub.2                                                                             CH.sub.2                                                                             CH.sub.2                                                                             CH.sub.2                                                                             CH.sub.2                                                                             CH.sub.2             __________________________________________________________________________

                                      TABLE 19                                    __________________________________________________________________________     ##STR238##                                                                   __________________________________________________________________________       ##STR239##                                                                          ##STR240##                                                                           ##STR241##                                                                           ##STR242##                                                                           ##STR243##                                                                           ##STR244##                                                                           ##STR245##                                                                           ##STR246##                                                                          ##STR247##           X                                                                                ##STR248##                                                                          ##STR249##                                                                           ##STR250##                                                                           ##STR251##                                                                           ##STR252##                                                                           ##STR253##                                                                           ##STR254##                                                                           ##STR255##                                                                          ##STR256##           Z CH.sub.2                                                                            (CH.sub.2).sub.2                                                                     CH.sub.2                                                                             (CH.sub.2).sub.2                                                                     CH.sub.2                                                                             (CH.sub.2).sub.2                                                                     (CH.sub.2).sub.3                                                                     CH.sub.2                                                                            (CH.sub.2).sub.2      __________________________________________________________________________

                                      TABLE 20                                    __________________________________________________________________________     ##STR257##                                                                   __________________________________________________________________________       ##STR258##                                                                           ##STR259##                                                                          ##STR260##                                                                           ##STR261##                                                                           ##STR262##                                                                           ##STR263##                                                                           ##STR264##                                                                           ##STR265##                                                                          ##STR266##           X                                                                                ##STR267##                                                                           ##STR268##                                                                          ##STR269##                                                                           ##STR270##                                                                           ##STR271##                                                                           ##STR272##                                                                           ##STR273##                                                                           ##STR274##                                                                          ##STR275##           Z (CH.sub.2).sub.3                                                                     CH.sub.2                                                                            (CH.sub.2).sub.2                                                                     (CH.sub.2).sub.3                                                                     CH.sub.2                                                                             (CH.sub.2).sub.2                                                                     (CH.sub. 2).sub.3                                                                    CH.sub.2                                                                            (CH.sub.2).sub.2      __________________________________________________________________________

                                      TABLE 21                                    __________________________________________________________________________     ##STR276##                                                                   __________________________________________________________________________     ##STR277##                                                                           ##STR278##                                                                           ##STR279##                                                                           ##STR280##                                                                           ##STR281##                                                                           ##STR282##                                                                           ##STR283##                                                                           ##STR284##                                                                           ##STR285##            ##STR286##                                                                           ##STR287##                                                                           ##STR288##                                                                           ##STR289##                                                                           ##STR290##                                                                           ##STR291##                                                                           ##STR292##                                                                           ##STR293##                                                                           ##STR294##            ##STR295##                                                                           CH.sub.2                                                                             (CH.sub.2).sub.2                                                                     (CH.sub.2).sub.3                                                                     CH.sub.2                                                                             (CH.sub.2).sub.2                                                                     (CH.sub.2).sub.3                                                                     CH.sub.2                                                                             (CH.sub.2).sub.2     __________________________________________________________________________

                                      TABLE 22                                    __________________________________________________________________________     ##STR296##                                                                   __________________________________________________________________________    ACH.sub.2                                                                            CH.sub.2                                                                             CH.sub.2                                                                             CH.sub.2                                                                             CH.sub.2                                                                             CH.sub.2                                                                             CH.sub.2                                                                             (CH.sub.2).sub.2                                                                     (CH.sub.2).sub.3       ##STR297##                                                                           ##STR298##                                                                           ##STR299##                                                                           ##STR300##                                                                           ##STR301##                                                                           ##STR302##                                                                           ##STR303##                                                                           ##STR304##                                                                           ##STR305##            ##STR306##                                                                           ##STR307##                                                                           ##STR308##                                                                           ##STR309##                                                                           ##STR310##                                                                           ##STR311##                                                                           ##STR312##                                                                           ##STR313##                                                                           ##STR314##            ##STR315##                                                                           CH.sub.2                                                                             (CH.sub.2).sub.2                                                                     (CH.sub.2).sub.3                                                                     CH.sub.2                                                                             (CH.sub.2).sub.2                                                                     (CH.sub.2).sub.3                                                                     CH.sub.2                                                                             CH.sub.2             __________________________________________________________________________

                                      TABLE 23                                    __________________________________________________________________________     ##STR316##                                                                   __________________________________________________________________________    R.sup.4                                                                         Et     Et     Et     Me   Et   n-Pr n-Bu                                                                                ##STR317##                                                                          CH.sub.2 CCH                A (CH.sub.2).sub.4                                                                     (CH.sub.2).sub.5                                                                     CHMe   CH.sub.2                                                                           CH.sub.2                                                                           CH.sub.2                                                                           CH.sub.2                                                                           CH.sub.2                                                                             CH.sub.2                    __________________________________________________________________________

                                      TABLE 24                                    __________________________________________________________________________     ##STR318##                                                                   __________________________________________________________________________    R.sup.3                                                                          Me Et n-Pr                                                                             n-Bu                                                                             n-Pentyl                                                                            ##STR319##                                                                          CH.sub.2 CCH                                                                         Me Et                                       R.sup.4                                                                          Et Et Et Et Et   Et     Et     H  H                                        __________________________________________________________________________

                                      TABLE 25                                    __________________________________________________________________________     ##STR320##                                                                   __________________________________________________________________________    R.sup.1                                                                          Me  Me  Me  Me   Me  Me  Me   Et  n-Pr                                     R.sup.2                                                                          OH  OH  OH  OH   OMe OEt O-n-Pr                                                                             OH  OH                                       R.sup.3                                                                          i-Pr                                                                              i-Bu                                                                              n-Bu                                                                              n-Pentyl                                                                           H   H   H    H   H                                        R.sup.4                                                                          H   H   H   H    Et  Et  Et   Et  Et                                       __________________________________________________________________________

                                      TABLE 26                                    __________________________________________________________________________     ##STR321##                                                                   __________________________________________________________________________    R.sup.1                                                                          n-Bu                                                                              n-Pentyl                                                                           Me       Me         Me                                            R.sup.6'                                                                         CO.sub.2 H                                                                        CO.sub.2 H                                                                          ##STR322##                                                                             ##STR323##                                                                               ##STR324##                                   __________________________________________________________________________

                                      TABLE 27                                    __________________________________________________________________________     ##STR325##                                                                   __________________________________________________________________________        ##STR326##                                                                              ##STR327##                                                                             ##STR328##                                                                               ##STR329##                                                                             ##STR330##                         R.sup.6'                                                                          ##STR331##                                                                              ##STR332##                                                                             ##STR333##                                                                               ##STR334##                                                                             ##STR335##                         __________________________________________________________________________

                                      TABLE 28                                    __________________________________________________________________________     ##STR336##                                                                   __________________________________________________________________________        ##STR337##                                                                              ##STR338##                                                                             ##STR339##                                                                             ##STR340##                                                                             ##STR341##                           R.sup.6'                                                                          ##STR342##                                                                              ##STR343##                                                                             ##STR344##                                                                             ##STR345##                                                                             ##STR346##                           __________________________________________________________________________

                                      TABLE 29                                    __________________________________________________________________________     ##STR347##                                                                   __________________________________________________________________________    R.sup.6                                                                          CH.sub.2 CO.sub.2 H                                                                  (CH.sub.2).sub.2 CO.sub.2 H                                                          (CH.sub.2).sub.3 CO.sub.2 H                                                           (CH.sub.2).sub.4 CO.sub.2 H                                                          CH.sub.2 CO.sub.2 Me                          __________________________________________________________________________

                                      TABLE 30                                    __________________________________________________________________________     ##STR348##                                                                   __________________________________________________________________________    R.sup.6                                                                          CH.sub.2 CO.sub.2 Et                                                                 ##STR349##                                                                                 ##STR350##                                                                          ##STR351##                                                                          ##STR352##                                 __________________________________________________________________________

                                      TABLE 31                                    __________________________________________________________________________     ##STR353##                                                                   __________________________________________________________________________    R.sup.6                                                                          ##STR354##                                                                          ##STR355##                                                                            ##STR356##                                                                            ##STR357##                                                                               ##STR358##                                __________________________________________________________________________

                                      TABLE 32                                    __________________________________________________________________________     ##STR359##                                                                   __________________________________________________________________________    R.sup.6                                                                           ##STR360##                                                                           ##STR361##                                                                            ##STR362##                                                                           ##STR363##                                                                           ##STR364##                                   __________________________________________________________________________

                                      TABLE 33                                    __________________________________________________________________________     ##STR365##                                                                   __________________________________________________________________________    R.sup.6                                                                          ##STR366##                                                                                 ##STR367##                                                                           ##STR368##                                                                          ##STR369##                                                                            ##STR370##                               __________________________________________________________________________

                                      TABLE 34                                    __________________________________________________________________________     ##STR371##                                                                   __________________________________________________________________________    R.sup.6                                                                          ##STR372##                                                                           ##STR373##                                                                            CH.sub.2 CONH.sub.2                                                                  CH.sub.2 CONHCH.sub.3                                                                 CH.sub.2 CONMe.sub.2                         __________________________________________________________________________

                                      TABLE 35                                    __________________________________________________________________________     ##STR374##                                                                   __________________________________________________________________________    R.sup.6                                                                         (CH.sub.2).sub.2 CONH.sub.2                                                           (CH.sub.2).sub.3 CONMe.sub.2                                                            ##STR375##                                                                              ##STR376##                                                                              ##STR377##                            __________________________________________________________________________

                                      TABLE 36                                    __________________________________________________________________________     ##STR378##                                                                   __________________________________________________________________________    R.sup.6                                                                           ##STR379##                                                                           ##STR380##                                                                           ##STR381##                                                                             ##STR382##                                                                           ##STR383##                                  __________________________________________________________________________

                                      TABLE 37                                    __________________________________________________________________________     ##STR384##                                                                   __________________________________________________________________________     ##STR385##                                                                        ##STR386##                                                                              ##STR387##                                                                            ##STR388##                                                                             ##STR389##                                                                            ##STR390##                            __________________________________________________________________________

                  TABLE 38                                                        ______________________________________                                         ##STR391##                                                                   ______________________________________                                        R.sup.1                                                                             Et         n-Pr   Me       Me   Me                                      R.sup.2                                                                             OH         OH     OMe      OEt  OH                                      R.sup.3                                                                             H          H      H        H    n-Pr                                    R.sup.4                                                                             Et         Et     Et       Et   H                                       ______________________________________                                    

                                      TABLE 39                                    __________________________________________________________________________     ##STR392##                                                                   __________________________________________________________________________    R.sup.2                                                                          OH     OMe    OMe     OH      OH                                           R.sup.3                                                                          n-Pr   n-Pr   n-Pr    H       H                                            R.sup.4                                                                          H      H      H       Et      Et                                           A  CH.sub.2                                                                             CH.sub.2                                                                             CH.sub.2                                                                              (CH.sub.2).sub.2                                                                      CH.sub.2                                     R.sup.5                                                                          H      H      H       H       Me                                           R.sup.6                                                                           ##STR393##                                                                           ##STR394##                                                                          (CH.sub.2).sub.2 CO.sub.2 H                                                           (CH.sub.2).sub.2 CO.sub.2 H                                                           (CH.sub.2).sub.2 CO.sub.2 H                  __________________________________________________________________________

                  TABLE 40                                                        ______________________________________                                         ##STR395##                                                                   ______________________________________                                        R.sup.5                                                                             Et       n-Pr   isoBu    sec-Bu                                                                              (CH.sub.2).sub.2 OH                      ______________________________________                                    

                                      TABLE 41                                    __________________________________________________________________________     ##STR396##                                                                   __________________________________________________________________________    R.sup.3                                                                          H       H      H      H      n-Pr                                          R.sup.4                                                                          Et      Et     Et     Et     H                                             R.sup.6                                                                          (CH.sub.2).sub.2 CO.sub.2 H                                                            ##STR397##                                                                           ##STR398##                                                                           ##STR399##                                                                           ##STR400##                                   __________________________________________________________________________

                                      TABLE 42                                    __________________________________________________________________________     ##STR401##                                                                   __________________________________________________________________________    R.sup.2                                                                         OMe     OH      OH      OH      OH                                          R.sup.3                                                                         n-Pr    H       H       H       H                                           R.sup.4                                                                         H       Et      Et      Et      Et                                             ##STR402##                                                                            ##STR403##                                                                            ##STR404##                                                                            ##STR405##                                                                            ##STR406##                                 R.sup.6                                                                          ##STR407##                                                                           (CH.sub.2).sub.2 CO.sub.2 H                                                            ##STR408##                                                                            ##STR409##                                                                            ##STR410##                                 __________________________________________________________________________

                                      TABLE 43                                    __________________________________________________________________________     ##STR411##                                                                   __________________________________________________________________________    R.sup.2                                                                         OH      OMe     OH      OH      OH                                          R.sup.3                                                                         n-Pr    n-Pr    H       H       H                                           R.sup.4                                                                         H       H       Et      Et      Et                                             ##STR412##                                                                            ##STR413##                                                                            ##STR414##                                                                            ##STR415##                                                                            ##STR416##                                 R.sup.6                                                                          ##STR417##                                                                            ##STR418##                                                                           (CH.sub.2).sub.2 CO.sub.2 H                                                            ##STR419##                                                                            ##STR420##                                 __________________________________________________________________________

                                      TABLE 44                                    __________________________________________________________________________     ##STR421##                                                                   __________________________________________________________________________    R.sup.2                                                                          OH      OH      OMe     OH      OH                                         R.sup.3                                                                          H       n-Pr    n-Pr    H       H                                          R.sup.4                                                                          Et      H       H       Et      Et                                         R.sup.6                                                                           ##STR422##                                                                            ##STR423##                                                                            ##STR424##                                                                            ##STR425##                                                                            ##STR426##                                __________________________________________________________________________

                                      TABLE 45                                    __________________________________________________________________________     ##STR427##                                                                   __________________________________________________________________________    R.sup.6                                                                          ##STR428##                                                                          ##STR429##                                                                                 ##STR430##                                                                                  ##STR431##                                                                          ##STR432##                          __________________________________________________________________________

                                      TABLE 46                                    __________________________________________________________________________     ##STR433##                                                                   __________________________________________________________________________    R.sup.1                                                                          Me      Et      Me      Me      Me                                         R.sup.6                                                                          (CH.sub.2).sub.2 OH                                                                   (CH.sub.2).sub.3 OH                                                                   (CH.sub.2).sub.4 OH                                                                    ##STR434##                                                                            ##STR435##                                __________________________________________________________________________

                                      TABLE 47                                    __________________________________________________________________________     ##STR436##                                                                   __________________________________________________________________________    R.sup.2                                                                         OH     O-n-Pr OH      OH      OH                                            R.sup.3                                                                         Me     H      H       H       H                                             R.sup.4                                                                         Me     H      Et      Et      Et                                            R.sup.5                                                                         H      H      H       Me      H                                             R.sup.6                                                                         (CH.sub.2).sub.2 CO.sub.2 H                                                          (CH.sub.2).sub.2 CO.sub.2 H                                                          CH(CH.sub.2 OH).sub.2                                                                 CH(CH.sub.2 OH).sub.2                                                                 CH.sub.2 CONHCH.sub.2 CO.sub.2 H              __________________________________________________________________________

Among the leukotriene B₄ antagonists thus obtained, the compound [I] canbe converted to a pharmaceutically acceptable salt form. Thepharmaceutically acceptable salts of these leukotriene B₄ antagonistscan be formed with pharmaceutically acceptable metal cation such assodium, potassium, magnesium and calcium, ammonium or amine cations.

The preparations of pharmaceutical compositions can be carried out byconventional methods. For example, leukotriene B₄ antagonists [I] may bemixed with carriers, diluents, lubricants, fillers and/or binders suchas lactose, sucrose, calcium phosphate, starch, talcum, casein,magnesium stearate, methyl cellulose, polyglycols, tragacanth and thelike, sometimes together with stabilizers and emulsifying agents. Theresulting mixture may be processed in a usual manner to tablets,capsules, pills, injections, ointment, suppositories and the like. In aclinical practice, the leukotriene B₄ antagonists [I] can beadministered orally, intranasally, intradermally or the like.

The daily dosage may vary depending upon the administration route,symptom, age or weight of the patient, and the usual oral dosage of theactive ingredient is between about 1 mg and about 1000 mg daily forhuman beings.

DESCRIPTION OF THE PREFERRED EMBODIMENTS

Practical and preferred embodiments of the present invention areillustrated in the following examples, which are not intended to limitthe scope of the invention.

REFERENCE EXAMPLE 1

5-Ethyl-2,4-dihydroxyacetophenone (0.97 g, 5.0 mmol) and methyl6-bromomethylpyridine-2-carboxylate (1.38 g, 5.8 mmol) were dissolved inan N,N-dimethylformamide solution (50 ml), and anhydrous potassiumcarbonate (480 mg) was added to the above solution, and the mixture wasstirred at room temperature for 16 hours. The reaction mixture waspoured into water and extracted with ethyl acetate (100 ml×3).

The extract was dried, concentrated and chromatographed on silica gel togive methyl6-[(4-acetyl-2-ethyl-5-hydroxyphenoxy)methyl]pyridine-2-carboxylate.

REFERENCE EXAMPLE 2

Methyl6-[(4-acetyl-2-ethyl-5-hydroxyphenoxy)methyl]pyridine-2-carboxylate (38mg, 12 mmol) was dissolved in a methanol solution (2 ml), and one normalsodium hydroxide (1 ml) was added to the above solution at 0° C., andthe mixture was stirred at room temperature for 1 hour. One-tenth normalpotassium bisulfate was titrated to the above solution until it becamepH2. Then, precipitated white crystals were separated by filtration, andwashed with water, and dried to give6-[(4-acetyl-2-ethyl-5-hydroxyphenoxy)methyl]pyridine-2-carboxylic acid.

REFERENCE EXAMPLE 3

3-n-Propyl-2,4-dihydroxyacetophenone (816 mg, 4.2 mmol) was added to amethanol solution (10 ml), sodium metal was added to the solution at 0°C., and the mixture was stirred for 30 min, and evaporated under reducedpressure, and dried to give a sodium salt of3-n-propyl-2,4-dihydroxyacetophenone. The salt was dissolved inN,N-dimethylformamide (10 ml), and it was added to aN,N-dimethylformamide solution (10 ml) ofmethyl-6-bromomethylpyridine-2-carboxylate (920 mg, 4.0 mmol) at roomtemperature, and the mixture was stirred for 1 hour.

The reaction mixture was poured into water, and normal potassiumbisulfate was titrated until it became pH3, and extracted with ethylacetate (100 ml×3). The extract was dried, concentrated andchromatographed on silica gel to give methyl6-[(4-acetyl-3-hydroxy-2-n-propylphenoxy)methyl]pyridine-2-carboxylate.

REFERENCE EXAMPLE 4

According to the procedure of Reference Example 2,6-[(4-acetyl-3-hydroxy-2-n-propylphenoxy)methyl]pyridine-2-carboxylicacid was obtained by hydrolysis of methyl6-[(4-acetyl-3-hydroxy-2-n-propylphenoxy)methyl]pyridine-2-carboxylate.

REFERENCE EXAMPLE 5

Anhydrous potassium carbonate (1.0 g) was added to aN,N-dimethylformamide solution (10 ml) of methyl6-[(4-acetyl-2-ethyl-5-hydroxyphenoxy)methyl]pyridine-2-carboxylate (500mg, 1.4 mmol) and methyliodide (5 ml), and the mixture was stirred at70° C. for 2 hours.

The reaction mixture was poured into water and extracted withethylacetate and washed with saturated aqueous sodium chloride. Then,the extract was dried, concentrated and chromatographed on silica gel togive methyl6-[(4-acetyl-2-ethyl-5-methoxyphenoxy)methyl]pyridine-2-carboxylate.

REFERENCE EXAMPLE 6

According to the procedure of Reference Example 2,6-[(4-acetyl-2-ethyl-5-methoxyphenoxy)methyl]pyridine-2-carboxylic acidwas obtained by hydrolysis of methyl6-[(4-acetyl-2-ethyl-5-methoxyphenoxy)methyl]pyridine-2-carboxylate.

REFERENCE EXAMPLE 7

According to the procedure of Reference Example 5, methyl6-[(4-acetyl-2-n-propyl-3-methoxyphenoxy)methyl]pyridine-2-carboxylatewas obtained from methyl6-[(4-acetyl-3-hydroxy-2-n-propylphenoxy)methyl]pyridine-2-carboxylate.

REFERENCE EXAMPLE 8

According to the procedure of Reference Example 2,6-[(4-acetyl-2-n-propyl-3-methoxyphenoxy)methyl]pyridine-2-carboxylicacid was obtained by hydrolysis of methyl6-[(4-acetyl-2-n-propyl-3-methoxyphenoxy)methyl]pyridine-2-carboxylate.

REFERENCE EXAMPLE 9 a compound included in formula [XVI]

A mixture of 6-methylpyridine-2-carboxylic acid (13.7 g, 100 mmol) andthionyl chloride (40 ml) was stirred at 70° C. for 1 hour. The mixturewas dried, and dichloromethane (40 ml) was added to the residue. Thesolution was added to a dichloromethane solution of2-amino-2-methyl-propanol (36.0 g, 400 mmol), and stirred. The mixturewas washed with water, and dried over anhydrous magnesium sulfate. Theextract was concentrated and chromatographed on silica gel to give anamide compound. 4,4-Dimethyl-2-oxazoline compound was obtained byreacting the amide compound and thionyl chloride in dichloromethane.4,4-Dimethyl-2-oxazoline compound was reacted with n-butyl lithium at-78° C. in anhydrous tetrahydrofuran, and chloroethyl phenyl ether (782mg, 5 mmol) was added. Purified alkylated compound was treated withethanol saturated with HCl to give ethyl6-(3-chloropropyl)pyridine-2-carboxylate.

REFERENCE EXAMPLE 10 a compound included in formula [II]

According to the procedure of Reference Examples 1,2,6-[3-(4-acetyl-2-ethyl-5-hydroxyphenoxy)propyl]pyridine-2-carboxylicacid was obtained from ethyl 6-(3-chloropropyl)pyridine-2-carboxylateand 5-ethyl-2,4-dihydroxyacetophenone.

                  TABLE 48                                                        ______________________________________                                               ##STR437##                                                             2                                                                                    ##STR438##                                                             3                                                                                    ##STR439##                                                             4                                                                                    ##STR440##                                                             ______________________________________                                    

                  TABLE 49                                                        ______________________________________                                                .sup.1 H-NMR δ ppm                                              ______________________________________                                        1   (solvent:CDCL.sub.3) 0.99(3H, J=7.4Hz), 1.62(2H, tq, J=7.4Hz,                 J=7.4Hz), 2.57(3H, s), 2.76(2H, t, J=7.4Hz), 4.04(3H, s),                     5.39(2H, s), 6.46(1H, d, J=8.9Hz), 7.59(1H, d, J=8.9Hz),                      7.79(1H, d, J=6.6Hz), 7.92(1H, dd, J=6.6Hz, J=7.9Hz),                         8.10(1H, d, J=7.9Hz)                                                      2   (solvent:CDCL.sub.3) 1.26(3H, t, J=7.6Hz), 2.59(3H, S),                       2.68(2H, q, J=7.6Hz), 5.30(2H, s), 6.43(1H, s), 7.51(1H, s),                  7.78(1H, d, J=6.9Hz), 8.04(1H, dd, J=6.9Hz, J=7.9Hz),                         8.22(1H, d, J=7.9Hz)                                                      3   (solvent:CDCL.sub.3) 0.99(3H, t, J=7.4Hz), 1.62(2H, tq, J=7.4Hz,              J=7.4Hz), 2.57(3H, s), 2.76(2H, t, J=7.4Hz), 4.04(3H, s),                     5.39(2H, s), 6.46(1H, d, J=8.9Hz), 7.59(1H, d, J=8.9Hz),                      7.79(1H, d, J=6.6Hz), 7.92(1H, dd, J=6.6Hz, J=7.9Hz),                         8.10(1H, d, J=7.9Hz)                                                      4   (solvent:CDCL.sub.3) 0.99(3H, t, J=7.4Hz), 1.62(2H, tq, J=7.4Hz,              J=7.4Hz), 2.57(3H, s), 2.76(2H, t, J=7.4Hz), 5.34(2H, s),                     6.45(1H, d, J=8.9Hz), 7.60(1H, d, J=8.9Hz), 7.79(1H, dd,                      J=1.0Hz, J=6.9Hz), 8.04(1H, dd, J=6.9Hz, J=7.4Hz),                            8.21(1H, dd, J=1.0Hz, J= 7.4Hz)                                           ______________________________________                                    

                  TABLE 50                                                        ______________________________________                                               ##STR441##                                                             6                                                                                    ##STR442##                                                             7                                                                                    ##STR443##                                                             8                                                                                    ##STR444##                                                             ______________________________________                                    

                  TABLE 51                                                        ______________________________________                                                .sup.1 H-NMR δ ppm                                              ______________________________________                                        5   (solvent:CDCL.sub.3) 1.24(3H, t, J=7.6Hz), 2.58(3H, s),                       2.70(2H, q, J=7.6Hz), 3.86(3H, s), 4.04(3H, s), 5.40(2H, s),                  7.72(1H, s), 7.79(1H, d, J=7.9Hz), 7.94(1H, dd, J=7.9Hz),                     J=7.6Hz), 8.11(1H, d, J=7.6Hz)                                            6   (solvent:CDCL.sub.3) 1.24(3H, t, J=7.4Hz), 2.57(3H, s),                       2.69(2H, q, J=7.4Hz), 3.90(3H, s), 5.40(2H, s), 6.64(1H, s),                  7.65(1H, s), 7.80(1H, d, J=7.3Hz), 8.01(1H, dd, J=7.6Hz,                      J=7.6Hz), 8.13(1H, d, J=7.9Hz)                                            7   (solvent:CDCL.sub.3) 1.02(3H, t, J=7.5Hz), 1.66(2H, q,                        J=7.6Hz), 2.61(3H, s), 2.75(2H, t, J=7.8Hz), 3.78(3H, s),                     5.31(2H, s), 6.70(1H, d, J=8.6Hz), 7.56(1H, d, J=8.9Hz),                      7.90(1H, d, J=7.9Hz),                                                         8.04(1H, dd, J=7.6Hz, J=7.9Hz), 8.21(1H, d, J=7.6Hz)                      8   (solvent:CDCL.sub.3) 1.02(3H, t, J=7.6Hz), 1.65(2H, q,                        J=7.7Hz), 2.62(3H, s), 2.75(2H, t, J=7.8Hz), 3.78(3H, s),                     5.31(2H, s), 6.70(1H, d, J=8.6Hz), 7.56(1H, d, J=8.9Hz),                      7.90(1H, d, J=7.9Hz), 8.04(1H, dd, J=7.6Hz, J=7.9Hz),                         8.21(1H, d, J=7.6Hz)                                                      ______________________________________                                    

EXAMPLE 1

A mixture of6-[(4-acetyl-2-ethyl-5-hydroxyphenoxy)methyl]pyridine-2-carboxylic acid(63 mg, 0.20 mmol), 1-ethyl-3-(3-dimethylaminopropyl)carbodiimidehydrochloride (40 mg, 0.20 mmol), 1-hydroxybenzotriazole (30 mg, 0.22mmol), 2-aminothiazole-4-carboxamide (35 mg, 0.24 mg) and triethylamine(20 mg, 0.20 mmol) in a mixed solution of dichloromethane (2 ml) andN,N-dimethylformamide (2 ml) was stirred at room temperature for 44hours. The reaction mixture was poured into water and extracted withethyl acetate (80 ml×3). The extract was dried over anhydrous magnesiumsulfate, concentrated under reduced pressure and chromatographed onsilica gel to give2-[6-[(4-acetyl-2-ethyl-5-hydroxyphenoxy)methyl]pyridine-2-carboxamide]thiazol-4-ylcarboxamide.

EXAMPLE 2˜35,62,88,90,92

According to the procedure of Example 1, the compounds (Example2˜35,62,88,90,92) were obtained.

EXAMPLE 36

Ethyl2-[6-[(4-acetyl-2-ethyl-5-hydroxyphenoxy)methyl]pyridine-2-carboxamide]thiazole-4-ylcarboxylate(24 mg, 0.05 mmol) was suspended in methanol (1.5 ml), followed byaddition of one-second normal sodium hydroxide (1.0 ml).

After the solution was stirred for 2 hr, it was made acidic withone-second normal potassium bisulfate. Precipitated crystals wereseparated by filtration, and washed with water, and dried to give2-[6-[(4-acetyl-2-ethyl-5-hydroxyphenoxy)methyl]pyridine-2-carboxamide]thiazol-4-ylcarboxylicacid.

EXAMPLE 37˜52,61,87,89,91

According to the procedure of Example 36, the compounds (Example 37˜52,61, 87, 89, 91) were obtained.

EXAMPLE 54˜56,64,67,68,70,72,74,76,78,80,82,84,86,94,96,100,102,104,106,108,112,114,115,116-121,123,126,127,138,141

According to the procedure of Example 1, the title compounds wereobtained.

EXAMPLE 53,57˜60,63,65,69,71,73,75,77,79,81,83,85,93,95,99,101,105,107,111,113,122,130

According to the procedure of Example 36, the title compounds wereobtained.

EXAMPLE 98

Ethyl2-[6-[(4-acetyl-2-ethyl-5-hydroxyphenoxy)methyl]pyridine-2-carboxamide]pyridine-6-ylcarboxylate(280 mg, 0.60 mM) was dissolved in dichloromethane (5 ml), followed byaddition of m-chloroperbenzoic acid (124 mg, 0.72 mM). After beingstirred at room temperature for 16 hours, the reaction mixture waswashed with aqueous sodium sulfite-sodium bicarbonate, dried overanhydrous magnesium sulfate, and concentrated under reduced pressure togive ethyl2-[6-[(4-acetyl-2-ethyl-5-hydroxyphenoxy)methyl]pyridine-2-carboxamide]pyridine-N-oxide-6-ylcarboxylate.

EXAMPLE 110,125,129,131,134,136,139,142

According to the procedure of Example 98, the title compounds wereobtained.

EXAMPLE 97,109,124,128,132,133,135,137,140

According to the procedure of Example 36, the title compounds wereobtained.

EXAMPLE 143˜178,212,214,216,218,222,225,226

According to the procedure of Example 1, the title compounds wereobtained.

EXAMPLE 179˜211,213,215,223,224

According to the procedure of Example 36, the title compounds wereobtained.

                  TABLE 52                                                        ______________________________________                                        Ex. No.                                                                              Structural formula                                                     ______________________________________                                                ##STR445##                                                            2                                                                                     ##STR446##                                                            3                                                                                     ##STR447##                                                            4                                                                                     ##STR448##                                                            5                                                                                     ##STR449##                                                            ______________________________________                                    

                  TABLE 53                                                        ______________________________________                                                .sup.1 H-NMR δ ppm                                              ______________________________________                                        1   (solvent:CDCL.sub.3) 1.28(3H, t, J=7.6Hz), 2.60(3H, s),                       2.71(2H, q, J=7.6Hz), 5.34(1H, s), 5.55(1H, bs), 6.48(1H, s),                 7.05(1H, bs), 7.52(1H, s), 7.77(1H, d, J=7.3Hz), 9.90(1H, s),                 8.04(1H, dd, J=6.6Hz, J=7.3Hz), 8.28(1H, d, J=7.3Hz),                         10.98(1H, bs), 12.70(1H, s)                                               2   (solvent:CDCL.sub.3) 1.27(3H, t, J=7.6Hz), 2.59(3H, s),                       2.70(2H, q, J=7.6Hz), 3.69(2H, s), 5.32(2H, s), 5.43(1H, bs),                 6.45(1H, s), 6.60(1H, bs), 6.86(1H, s), 7.51(1H, s),                          7.74(1H, d, J=6.9Hz), 8.02(1H, t, J=6.9Hz), 8.27(1H, d,                       J=6.9Hz), 12.68(1H, s)                                                    3   (solvent:CDCL.sub.3) 1.26(3H, t, J=7.6Hz), 2.58(3H, s),                       2.69(2H, q, J=7.6Hz), 3.70(2H, s), 3.81(3H, s), 5.39(1H, s),                  5.43(1H, bs), 6.46(1H, s), 6.70(1H, bs), 6.88(1H, s), 7.49(1H, s),            7.64(1H, dd, J=1.0Hz, J=7.9Hz), 7.79(1H, dd, J=7.6Hz,                         J=7.9Hz), 7.95(1H, dd, J=1.0Hz, J=7.6Hz), 12.65(1H, s)                    4   (solvent:CDCL.sub.3) 1.26(3H, t, J=7.6Hz), 1.44(3H, t, J=6.9Hz),              2.58(3H, s), 2.69(2H, q, J=7.6Hz), 3.69(2H, S), 4.36(2H, q,                   J=6.9Hz) 5.25(1H, s), 5.44(1H, bs), 6.43(1H, s), 6.67(1H, bs),                6.89(1H, s), 7.49(1H, s), 7.64(1H, d, J=7.9Hz), 7.74(1H, d,                   J=6.9Hz), 7.94(1H, dd, J=6.9Hz, J=7.9Hz), 12.66(1H, s)                    5   (solvent:CDCL.sub.3) 0.78(6H, d, J=6.6Hz), 1.26(3H, t,                        J=7.6Hz), 2.0-2.2(1H, m), 2.58(3H, s), 2.68(2H, q, J=7.6Hz),                  3.66(2H, s), 4.33(2H, d, J=7.3Hz), 5.21(2H, s), 5.84(1H, bs),                 6.42(1H, s), 6.60(1H, bs), 6.88(1H, s), 7.49(1H, s), 7.62(1H, d,              J=7.6Hz), 7.74(1H, d, J=7.9Hz), 7.93(1H, dd, J=7.6Hz,                         J=7.9Hz), 12.66(1H, s)                                                    ______________________________________                                    

                  TABLE 54                                                        ______________________________________                                        Ex.                                                                           No.  Structural formula                                                       ______________________________________                                              ##STR450##                                                              7                                                                                   ##STR451##                                                              8                                                                                   ##STR452##                                                              9                                                                                   ##STR453##                                                              10                                                                                  ##STR454##                                                              ______________________________________                                    

                  TABLE 55                                                        ______________________________________                                                .sup.1 H-NMR δ ppm                                              ______________________________________                                        6    (solvent:CDCL.sub.3) 1.28(3H, t, J=7.6Hz), 2.59(3H, s),                       2.70(2H, q, J=7.6Hz), 2.84(3H, d, J=5.0Hz), 3.67(2H, s),                      5.33(2H, s), 6.45(1H, s), 6.48(1H, bs), 6.85(1H, s),                          7.51(1H, s), 7.74(1H, d, J=6.6Hz), 8.02(1H, t,                                J=6.6Hz), 8.27(1H, d, J=6.6Hz), 11.06(1H, bs),                                12.70(1H, s)                                                             7    (solvent:CDCL.sub.3) 1.27(3H, t, J=7.6Hz), 2.59(3H, s),                       2.70(2H, q, J=7.6Hz), 3.01(3H, s), 3.11(1H, s), 3.83(2H, s),                  5.28(2H, s), 6.43(1H, s), 6.86(1H, b), 7.51(1H, s),                           7.72(1H, dd, J=1.0Hz, J=7.9Hz), 8.00(1H, t, J=7.9Hz),                         8.25(1H, dd, J=1.0Hz, J=7.9Hz), 11.08(1H, bs),                                12.70(1H, s)                                                             8    (solvent:CDCL.sub.3) 1.15(6H, d, J=6.6Hz), 1.27(3H, t,                        J=7.6Hz), 2.59(3H, s), 2.70(2H, q, J=7.6Hz), 3.63(2H, s),                     4.0-4.2(1H, m), 5.32(1H, s), 6.06(1H, bs), 6.45(1H, s),                       6.85(1H, s), 7.51(1H, s), 7.74(1H, d, J=7.9Hz), 8.02(1H,                      t, J=7.9Hz), 8.27(1H, d, J=7.9Hz), 11.06(1H, bs),                             12.70(1H, s)                                                             9    (solvent:CDCL.sub.3) 1.27(3H, t, J=7.6Hz), 1.31(3H, s),                       1.34(3H, s), 2.59(3H, s), 2.70(2H, q, J=7.6Hz), 3.1-3.2(1H,                   m), 5.30(2H, s), 6.44(1H, s),  6.62(1H, s), 7.51(1H, s),                      7.71(1H, d, J=7.9Hz), 7.99(1H, dd, J=6.6Hz, J=7.9Hz),                         8.26(1H, d, J=6.6Hz), 11.05(1H, bs), 12.67(1H, s)                        10   (solvent:CDCL.sub.3) 1.23(3H, t, J=7.6Hz), 2.60(3H, s),                       2.65(2H, q, J=7.6Hz), 5.49(2H, s), 6.64(1H, s),                               7.35-7.55(2H, m), 7.6-7.8(3H, m), 8.0-8.3(5H, m),                             10.59(1H, bs), 12.60(1H, s)                                              ______________________________________                                    

                  TABLE 56                                                        ______________________________________                                        Ex. No.                                                                              Structural formula                                                     ______________________________________                                        11                                                                                    ##STR455##                                                            12                                                                                    ##STR456##                                                            13                                                                                    ##STR457##                                                            14                                                                                    ##STR458##                                                            15                                                                                    ##STR459##                                                            ______________________________________                                    

                  TABLE 57                                                        ______________________________________                                                .sup.1 H-NMR δ ppm                                              ______________________________________                                        11   (solvent:CDCL.sub.3) 1.22(3H, t, J=7.6Hz), 2.58(3H, s),                       2.67(2H, q, J=7.6Hz), 5.49(1H, s), 6.64(1H, s), 7.53(1H, bs),                 7.71(1H, s), 7.80-7.85(1H, m), 8.1-8.4(5H, m),                                8.85-8.90(1H, m), 10.63(1H, bs), 12.56(1H, s)                            12   (solvent:CDCL.sub.3) 1.20(3H, t, J=7.6Hz), 2.58(2H, s),                       2.64(2H, q, J=7.6Hz), 5.47(2H, s), 6.62(1H, s), 7.30(2H, s),                  7.71(1H, s), 7.75-7.90(3H, m), 8.0-8.2(4H, m), 10.75(1H, bs),                 12.56(1H, s)                                                             13   (solvent:CDCL.sub.3) 1.00(3H, t, J=7.4Hz),                                    1.63(2H, tq, J=7.4Hz, J=7.4Hz), 2.58(3H, s), 2.77(2H, t,                      J=7.4Hz), 3.69(2H, s), 5.36(2H, s), 5.40(1H, bs), 6.47(1H, d,                 J=9.2Hz), 6.50(1H, bs), 6.87(1H, s), 7.62(1H, d, J=9.2Hz),                    7.76(1H, d, J=7.9Hz, 8.02(1H, dd, J=7.9Hz, J=7.9Hz),                          8.26(1H, d, J=7.9Hz)                                                     14   (solvent:CDCL.sub.3) 1.27(3H, t, J=7.6Hz) 1.43(3H, t,                         J=7.1Hz), 2.59(3H, s), 2.70(2H, q, J=7.6Hz), 4.45(2H, q,                      J=7.1Hz), 5.28(1H, s), 6.43(1H, s), 7.52(1H, s), 7.73(1H, d,                  J=7.9Hz), 7.94(1H, d, J=0.7Hz), 8.01(1H, t, J=7.9Hz),                         8.25(1H, d, J=7.9Hz), 11.32(1H, bs), 12.66(1H, s)                        15   (solvent:CDCL.sub.3 ) 1.27(3H, t, J=7.6Hz), 1.30(3H, t,                       J=7.3Hz), 2.59(3H, s), 2.70(2H, q, J=7.6Hz), 3.76(2H, d,                      J=0.7Hz), 4.22(2H, q, J=7.3Hz), 5.28(1H, s), 6.43(1H, s),                     6.90(1H, d, J=0.7Hz), 7.51(1H, s), 7.72(1H, d, J=7.9Hz),                      8.00(1H, dd, J=7.6Hz, J=7.9Hz), 8.25(1H, d, J=7.6Hz),                         11.11(1H, bs), 12.67(1H, s)                                              ______________________________________                                    

                                      TABLE 58                                    __________________________________________________________________________    Ex. No.                                                                            Structural formula                                                       __________________________________________________________________________    16                                                                                  ##STR460##                                                              17                                                                                  ##STR461##                                                              18                                                                                  ##STR462##                                                              19                                                                                  ##STR463##                                                              20                                                                                  ##STR464##                                                              __________________________________________________________________________

                  TABLE 59                                                        ______________________________________                                                .sup.1 H-NMR δ ppm                                              ______________________________________                                        16   (solvent:CDCL.sub.3) 1.25(3H, t, J=7.3Hz), 1.27(3H, t,                        J=7.4Hz), 2.59(3H, s), 2.65-2.80(4H, m), 3.05(2H, t,                          J=7.3Hz), 4.15(2H, q, J=7.3Hz), 5.30(2H, s), 6.44(1H, s),                     6.69(1H, s), 7.51(1H, s), 7.71(1H, d, J=7.7Hz), 7.97(1H, t,                   J=7.7Hz), 8.24(1H, d, J=7.7Hz), 11.05(1H, bs),                                12.67(1H, s)                                                             17   (solvent:CDCL.sub.3) 1.27(3H, t, J=7.6Hz), 1.43(3H, t,                        J=7.1Hz), 2.59(3H, s), 2.70(2H, q, J=7.6Hz), 4.45(2H, q,                      J=7.1Hz), 5.28(1H, s) 6.43(1H, s), 7.52(1H, s), 7.73(1H, d,                   J=7.9Hz), 7.94(1H, d, J=0.7Hz), 8.01(1H, t, J=7.9Hz),                         8.25(1H, d, J=7.9Hz), 11.32(1H, bs), 12.66(1H, s)                        18   (solvent:CDCL.sub.3) 1.26(3H, t, J=7.6Hz), 1.28(3H, t,                        J=7.1Hz), 1.40(3H, t, J=6.9Hz), 2.58(3H, s), 2.69(2H, q,                      J=7.6Hz), 3.76(2H, d, J=0.7Hz), 4.20(2H, q, J=7.1Hz),                         4.32(2H, q, J=6.9Hz), 5.25(1H, s), 6.44(1H, s), 6.92(1H, s),                  7.49(1H, s), 7.62(1H, d, J=7.6Hz), 7.70(1H, d, J=6.9Hz),                      7.92(1H, dd, J=6.9Hz, J=7.6Hz), 12.65(1H, s)                             19   (solvent:CDCL.sub.3) 0.76(6H, d, J=6.6Hz), 1.26(3H, t,                        J=7.6Hz), 1.27(3H, t, J= 7.1Hz), 2.0-2.2(1H, m),                              2.58(3H, s), 2.68(2H, q, J=7.6Hz), 3.74(2H, s), 4.18(2H, d,                   J=7.1Hz), 4.28(2H, d, J=6.9Hz), 5.21(2H, s), 6.43(1H, s),                     6.91(1H, s), 7.49(1H, s), 7.58(1H, d, J=7.9Hz), 7.71(1H, d,                   J=7.9Hz), 7.90(1H, t, J=7.9Hz), 12.63(1H, s)                             20   (solvent:CDCL.sub.3) 1.27(3H, t, J=7.4Hz), 1.29(3H, t,                        J=7.3Hz), 2.33(3H, s), 2.59(3H, s), 2.69(2H, q, J=7.4Hz),                     3.73(2H, s), 4.20(2H, q, J=7.3Hz), 5.27(2H, s), 6.43(1H, s),                  7.51(1H, s), 7.71(1H, d, J=7.9Hz), 7.99(1H, t, J=7.9Hz),                      8.24(1H, d, J=7.9Hz), 10.98(1H, bs), 12.67(1H, s)                        ______________________________________                                    

                                      TABLE 60                                    __________________________________________________________________________    Ex. No.                                                                            Structural formula                                                       __________________________________________________________________________    21                                                                                  ##STR465##                                                              22                                                                                  ##STR466##                                                              23                                                                                  ##STR467##                                                              24                                                                                  ##STR468##                                                              25                                                                                  ##STR469##                                                              __________________________________________________________________________

                  TABLE 61                                                        ______________________________________                                                .sup.1 H-NMR δ ppm                                              ______________________________________                                        21   (solvent:CDCL.sub.3) 1.27(3H, t, J=6.7Hz),                                    1.32(3H, t, J=7.1Hz), 2.59(3H, s), 2.71(2H, J=7.1Hz),                         4.16(2H, s), 4.27(2H, q, J=7.6Hz) 5.32(2H, s), 6.44(1H, s),                   7.52(1H, s), 7.75(1H, d, J=7.6Hz), 8.02(1H, t, J=7.6Hz),                      8.26(1H, d, J=7.6Hz), 11.21(1H, bs), 12.67(1H, s)                        22   (solvent:CDCL.sub.3) 1.27(3H, t, J=7.4Hz), 2.58(3H, s),                       2.70(2H, q, J=7.4Hz), 2.93(2H, t, J=7.3Hz), 3.40(2H, t,                       J=7.3Hz), 3.73(3H, s), 5.32(2H, s), 6.43(1H, s), 7.51(1H, s),                 7.75(1H, d, J=7.9Hz), 8.01(1H, t, J=7.9Hz), 8.24(1H, d,                       J=7.9Hz), 11.18(1H, bs), 12.66(1H, s)                                    23   (solvent:CDCL.sub.3) 1.27(3H, t, J=7.3Hz), 1.27(3H, t,                        J=7.3Hz), 2.59(3H, s), 2.70(2H, q, J=7.3Hz), 3.66(2H, s),                     4.17(2H, q, J=7.3Hz) 5.32(2H, s), 6.52(1H, s), 7.0-7.1(1H,                    m), 7.3-7.4(1H, m), 7.51(1H, s), 7.65-7.7(2H, m), 7.97(1H,                    t, J=7.7Hz), 8.26(1H, dd, J=1.0Hz, J=7.7Hz), 9.92(1H,                         bs), 12.68(1H, s)                                                        24   (solvent:CDCL.sub.3) 1.26(3H, t, J=7.1Hz), 1.27(3H, t,                        J=7.6Hz), 2.59(3H, s), 2.70(2H, q, J=7.6Hz), 3.62(2H, s),                     4.16(2H, q, J=7.1Hz) 5.32(2H, s), 6.51(1H, s), 7.32(1H, d,                    J=8.6Hz), 7.51(1H, s), 7.67(1H, d, J=7.3Hz), 7.75(1H, d,                      J=8.6Hz), 7.98(1H, dd, J=7.3Hz, J=7.6Hz), 8.27(1H, d,                         J=7.6Hz), 9.90(1H, bs), 12.68(1H, s)                                     25   (solvent:CDCL.sub.3) 1.28(3H, t, J=7.6Hz), 1.29(3H, t,                        J=7.3Hz), 2.59(3H, s), 2.71(2H, q, J=7.6Hz), 3.80(2H, s),                     4.21(2H, q, J=7.3Hz) 5.34(2H, s), 6.47(1H, s), 7.09(1H, d,                    J=6.9Hz), 7.51(1H, s), 7.65-7.85(2H, m), 7.97(1H, t,                          J=7.6Hz), 8.26(1H, t, J=7.6Hz), 8.30(1H, t, J=7.6Hz),                         10.37(1H, bs), 12.66(1H, s)                                              ______________________________________                                    

                                      TABLE 62                                    __________________________________________________________________________    Ex. No.                                                                            Structural formula                                                       __________________________________________________________________________    26                                                                                  ##STR470##                                                              27                                                                                  ##STR471##                                                              28                                                                                  ##STR472##                                                              29                                                                                  ##STR473##                                                              30                                                                                  ##STR474##                                                              __________________________________________________________________________

                  TABLE 63                                                        ______________________________________                                                .sup.1 H-NMR δ ppm                                              ______________________________________                                        26   (solvent:CDCL.sub.3) 1.25(3H, t, J=7.3Hz), 1.30(3H, t,                        J=7.3Hz), 2.59(3H, s), 2.71(2H, q, J=7.5Hz), 3.77(2H, s),                     3.92(3H, s), 4.22(2H, q, J=7.5Hz), 5.32(2H, s), 6.50(1H, s),                  6.91(1H, s), 7.73(1H, s), 7.80(1H, d, J=7.6Hz), 8.03(1H, dd,                  J=7.9Hz, J=7.6Hz), 8.24(1H, d, J=7.6Hz), 11.18(1H, s)                    27   (solvent:CDCL.sub.3) 1.26(3H, t, J=7.6Hz), 1.28(3H, t,                        J=7.4Hz), 2.59(3H, s), 2.72(2H, q, J=7.5Hz), 3.80(2H, s),                     3.92(3H, s), 4.21(2H, q, J=7.5Hz), 5.38(2H, s), 6.57(1H, s),                  7.10(1H, dd, J=7.0Hz, J=0.7Hz), 7.73(1H, s), 7.76(1H, dd,                     J=8.3Hz, J=7.9Hz), 7.77(1H, dd, J=7.9Hz, J=1.0Hz),                            8.00(1H, dd, J=7.6Hz, J=7.9Hz), 8.27(1H, dd, J=7.9Hz,                         J=1.0Hz), 8.37(1H, d, J=8.3Hz), 10.40(1H, s)                             28   (solvent:CDCL.sub.3) 1.00(3H, t, J=7.4Hz), 1.30(3H, t,                        J=7.1Hz), 1.63 (2H, tq, J=7.9Hz, J=7.3Hz), 2.58(3H, s),                       2.77(2H, t, J=7.6Hz), 3.77(2H, s), 4.22(2H, q, J=7.0Hz),                      5.32(1H, s) 6.46(1H, d, J=8.9Hz), 6.91(1H, s), 7.62(1H, d,                    J=8.9Hz), 7.74(1H, d, J=7.9Hz), 8.00(1H, dd, J=7.6Hz,                         J= 7.9Hz), 8.24(1H, dd, J=7.6Hz, J=0.6Hz)                                29   (solvent:CDCL.sub.3) 1.00(3H, t, J=7.4Hz), 1.29(3H, t,                        J=7.2Hz), 1.64(2H, tq, J=7.6Hz, J=7.2Hz), 2.58(3H, s),                        2.78(2H, t, J=7.2Hz), 3.81(2H, s), 4.21(2H, q, J=7.0Hz),                      5.38(2H, s), 6.50(1H, d, J=8.9Hz), 7.10(1H, dd, J=7.3Hz,                      J=0.7Hz), 7.62(1H, d, J=8.9Hz), 7.70(1H, d, J=7.9Hz),                         7.76(1H, dd, J=8.0Hz, J=7.9Hz), 7.97(1H, dd, J=7.9Hz,                         J=7.6Hz), 8.25(1H, d, J=6.9Hz), 8.36(1H, d, J=7.6Hz)                     30   (solvent:CDCL.sub.3) 1.03(3H, t, J=7.3Hz),                                    1.64(2H, tq, J=7.6Hz, J=7.8Hz), 2.59(3H, s), 2.74(2H, t,                      J=8.0Hz), 3.78(3H, s), 3.82(2H, s), 5.31(2H, s), 6.71(1H, d,                  J=8.9Hz), 6.83(1H, s), 7.53(1H, d, J=8.9Hz), 7.70(1H, d,                      J=7.6Hz), 7.97(1H, dd, J=7.6Hz, J=7.9Hz), 8.19(1H, d,                         J=7.6Hz)                                                                 ______________________________________                                    

                                      TABLE 64                                    __________________________________________________________________________    Ex. No.                                                                            Structural formula                                                       __________________________________________________________________________    31                                                                                  ##STR475##                                                              32                                                                                  ##STR476##                                                              33                                                                                  ##STR477##                                                              34                                                                                  ##STR478##                                                              35                                                                                  ##STR479##                                                              __________________________________________________________________________

                  TABLE 65                                                        ______________________________________                                                .sup.1 H-NMR δ ppm                                              ______________________________________                                        31   (solvent:CDCL.sub.3) 1.03(3H, t, J=7.3Hz),                                    1.65(2H, tq, J=7.6Hz, J=7.9Hz), 2.63(3H, s), 2.76(2H, t,                      J=7.6Hz), 3.79(3H, s), 3.90(2H, s), 5.37(2H, s), 6.81(1H, d,                  J=8.6Hz), 7.06(1H, d, J=7.6Hz), 7.59(1H, d, J=8.9Hz),                         7.75(1H, d, J=6.9Hz), 7.83(1H, dd, J=7.9Hz, J=7.9Hz),                         8.01(1H, dd, J=7.9Hz, J=7.9Hz), 8.28(1H, d, J=6.9Hz),                         8.37(1H, d, J=7.9Hz)                                                     32   (solvent:CDCL.sub.3) 1.27(3H, t, J=7.6Hz), 1.28(3H, t,                        J=7.1Hz), 2.59(3H, s), 2.71(2H, q, J=7.6Hz), 3.72(2H, s),                     4.17(2H, q, J=7.3Hz) 5.32(2H, s), 6.43(1H, s), 6.89(1H, s),                   7.51(1H, s), 7.67(1H, dd, J=0.7Hz, J=8.2Hz), 8.29(1H, dd,                     J=2.3Hz, J=8.2Hz), 9.14(1H, dd, J=0.7Hz, J=2.3Hz),                            9.58(1H, bs), 12.66(1H, s)                                               33   (solvent:CDCL.sub.3) 1.27(3H, t, J=7.6Hz), 1.32(3H, t,                        J=7.3Hz), 2.59(3H, s), 2.70(2H, q, J=7.6Hz), 4.30(2H, q,                      J=7.3Hz), 4.68(2H, s) 5.32(2H, s), 6.51(1H, s), 6.70-                         6.80(1H, m), 7.25-7.35(2H, m) 7.51(1H, s), 7.55-7.65(1H,                      m), 7.68(1H, d, J=7.6Hz), 7.98(1H, dd, J=6.6Hz,                               J=7.6Hz), 8.26(1H, d, J= 6.6Hz), 9.90(1H, bs),                                12.67(1H, s)                                                             34   (solvent:CDCL.sub.3) 1.27(3H, t, J=7.6Hz), 1.31(3H, t,                        J=7.3Hz), 2.59(3H, s), 2.70(2H, q, J=7.6Hz), 4.26(2H, q,                      J=7.3Hz), 4.63(2H, s) 5.31(2H, s), 6.51(1H, s), 6.96(2H, d,                   J=9.1Hz), 7.51(1H, s), 7.66(1H, d, J=8.6Hz), 7.71(2H, d,                      J=9.1Hz), 7.97(1H, dd, J=7.6Hz, J=8.6Hz), 8.26(1H, d,                         J=7.6Hz), 9.82(1H, s), 12.67(1H, s)                                      35   (solvent:CDCL.sub.3) 1.27(3H, t, J=7.3Hz), 1.27(3H, t,                        J=7.3Hz), 2.59(3H, s), 2.70(2H, q, J=7.6Hz), 3.73(2H, s),                     4.07(2H, d, J=5.3Hz) 4.20(2H, q, J=7.3Hz), 5.32(2H, s),                       6.45(1H, s), 6.88(1H, s), 7.03(1H, b), 7.51(1H, s), 7.74(1H,                  dd, J=1.0Hz, J=7.6Hz), 8.01(1H, dd, J=7.6Hz, J=7.9Hz),                        8.25(1H, dd, J=1.0Hz, J=7.9Hz), 11.08(1H, bs),                                12.67(1H, s)                                                             ______________________________________                                    

                                      TABLE 66                                    __________________________________________________________________________    Ex. No.                                                                            Structural formula                                                       __________________________________________________________________________    36                                                                                  ##STR480##                                                              37                                                                                  ##STR481##                                                              38                                                                                  ##STR482##                                                              39                                                                                  ##STR483##                                                              40                                                                                  ##STR484##                                                              __________________________________________________________________________

                  TABLE 67                                                        ______________________________________                                                .sup.1 H-NMR δ ppm                                              ______________________________________                                        36   (solvent:DMSO-d.sub.6) 1.20(3H, J=7.6Hz), 2.59(3H, s),                        2.63(2H, q, J=7.6Hz), 5.44(2H, s), 6.71(1H, s), 7.45(1H, s),                  7.66(1H, S), 7.7-7.8(1H, m), 8.10-8.20(2H, m), 12.60(1H, bs)             37   (solvent:DMSO-d.sub.6) 1.21(3H, t, J=7.6Hz), 2.58(3H, s),                     2.65(2H, q, J=7.6Hz), 3.67(2H, s), 5.46(2H, s), 6.63(1H, s),                  7.11(1H, s), 7.70(1H, s), 7.78(1H, dd, J=1.3Hz, J=7.3Hz),                     12.04(1H, bs), 12.55(1H, s)                                              38   (solvent:DMSO-d.sub.6) 1.21(3H, t, J=7.4Hz), 2.59(3H, s),                     2.55-2.75(4H, m), 2.89(2H, t, J=7.6Hz), 5.47(2H, s),                          6.63(1H, s), 6.95(1H, s), 7.70(1H, s), 7.78(1H, d,                            J=7.3Hz), 8.10-8.20(2H, m), 11.94(1H, bs), 12.57(1H, s)                  39   (solvent:DMSO-d.sub.6) 1.21(3H, t, J=7.4Hz), 2.58(3H, s),                     2.65(2H, q, J=7.4Hz), 4.15(2H, s), 5.47(2H, s), 6.63(1H, s),                  7.70(1H, s), 7.80(1H, d, J=6.9Hz), 8.10-8.20(2H, m),                          12.50(1H, bs), 12.56(1H, s)                                              40   (solvent:DMSO-d.sub.6) 1.21(3H, t, J=7.4Hz), 2.59(3H, s),                     2.55-2.75(4H, m), 2.89(2H, t, J=7.6Hz), 5.47(2H, s),                          6.63(1H, s), 6.95(1H, s), 7.70(1H, s), 7.78(1H, d, J=7.3Hz),                  8.10-8.20(2H, m), 11.94(1H, bs), 12.57(1H, s)                            ______________________________________                                    

                                      TABLE 68                                    __________________________________________________________________________    Ex. No.                                                                            Structural formula                                                       __________________________________________________________________________    41                                                                                  ##STR485##                                                              42                                                                                  ##STR486##                                                              43                                                                                  ##STR487##                                                              44                                                                                  ##STR488##                                                              45                                                                                  ##STR489##                                                              __________________________________________________________________________

                  TABLE 69                                                        ______________________________________                                                .sup.1 H-NMR δ ppm                                              ______________________________________                                        41   (solvent:DMSO-d.sub.6) 1.20(3H, t, J=7.6Hz), 2.58(3H, s),                     2.65(2H, q, J=7.6Hz), 3.58(1H, s), 5.47(2H, s), 6.63(1H, s),                  7.04(1H, d, J=7.9Hz), 7.33(1H, m), 7.7-7.8(4H, m),                            8.1-8.2(2H, m), 10.41(1H, s), 12.56(1H, s)                               42   (solvent:DMSO-d.sub.6) 1.20(3H, t, J=7.6Hz), 2.58(3H, s),                     2.65(2H, q, J=7.6Hz), 5.46(2H, s), 6.62(1H, s), 7.27(2H, d,                   J=8.2Hz) 7.65-7.85(4H, m), 8.05-8.20(2H, m),                                  8.10-8.20(2H, m), 10.40(1H, s) 12.56(1H, bs)                             43   (solvent:DMSO-d.sub.6) 1.23(3H, t, J=7.6Hz), 2.58(3H, s),                     2.67(2H, q, J=7.6Hz), 3.71(2H, s), 5.49(2H, s), 6.65(1H, s),                  7.17(1H, d, J=6.9Hz), 7.69(1H, s), 7.75-7.95(2H, m),                          8.10-8.20(3H, m), 10.33(1H, s), 12.55(1H, bs)                            44   (solvent:CDCL.sub.3) 1.25(3H, t, J=7.4Hz), 2.57(3H, s),                       2.70(2H, q, J=7.2Hz), 3.83(2H, s), 3.89(3H, s), 5.35(2H, s),                  6.52(1H, s), 6.88(1H, s), 7.70(1H, s), 7.81(1H, d, J=7.6Hz),                  8.03(1H, dd, J=7.9Hz, J=7.6Hz), 8.24(1H, d, J=7.6Hz)                     45   (solvent:CDCL.sub.3) 1.26(3H, t, J=6.7Hz), 2.59(3H, s),                       2.72(2H, q, J=6.9Hz), 3.91(2H, s), 3.93(3H, s), 5.39(2H, s),                  6.55(1H, s), 7.07(1H, d, J=7.3Hz), 7.74(1H, s), 7.83(1H, d,                   J=6.6Hz) 7.86(1H, dd, J=7.8Hz, J=7.6Hz), 8.04(1H, dd,                         J=7.9Hz, J=7.9Hz), 8.29(1H, d, J=6.6Hz), 8.41(1H, d,                          J=8.3Hz)                                                                 ______________________________________                                    

                                      TABLE 70                                    __________________________________________________________________________    Ex. No.                                                                            Structural formula                                                       __________________________________________________________________________    46                                                                                  ##STR490##                                                              47                                                                                  ##STR491##                                                              48                                                                                  ##STR492##                                                              49                                                                                  ##STR493##                                                              50                                                                                  ##STR494##                                                              __________________________________________________________________________

                  TABLE 71                                                        ______________________________________                                                .sup.1 H-NMR δ ppm                                              ______________________________________                                        46   (solvent:DMSO-d.sub.6) 0.92(3H, t, J=7.3Hz), 1.55(2H,                         tq, J=6.9Hz, J=7.7Hz), 2.52(3H, s), 2.67(2H, t,                               J=7.6Hz), 3.67(2H, s), 5.50(2H, s), 6.77(1H, d, J=9.2Hz),                     7.11(1H, s), 7.76(1H, d, J=7.2Hz) 7.81(1H, d, J=8.9Hz),                       8.11(1H, dd, J=7.6Hz, J=7.6Hz), 8.15(1H, d, J=7.6Hz)                     47   (solvent:CDCL.sub.3) 1.00(3H, t, J=7.4Hz), 1.64(2H, tq,                       J=7.6Hz, J=7.3Hz), 2.59(3H, s), 2.78(2H, t, J=7.6Hz),                         3.91(2H, s), 5.40(2H, s), 6.55(1H, d, J=8.9Hz), 7.07(1H, d,                   J=6.6Hz), 7.63(1H, d, J=8.2Hz), 7.77(1H, d, J=6.9Hz),                         7.85(1H, dd, J=7.9Hz, J=7.9Hz), 8.02(1H, dd, J=7.6Hz,                         J=7.9Hz), 8.27(H, d, J=6.9Hz), 8.39(1H, d, J=8.3Hz)                      48   (solvent:CDCL.sub.3) 1.03(3h, t, J=7.3Hz),                                    1.64(2H, tq, J=7.6Hz, J=7.8Hz), 2.59(3H, s), 2.74(2H, t,                      J=8.0Hz), 3.78(3H, s), 3.82(2H, s), 5.31(2H, s), 6.71(1H, d,                  J=8.9Hz), 6.83(1H, s), 7.53(1H, d, J=8.9Hz), 7.70(1H, d,                      J=7.6Hz), 7.97(1H, dd, J=7.6Hz, J=7.9Hz), 8.19(1H, d,                         J=7.6Hz)                                                                 49   (solvent:CDCL.sub.3) 1.03(3H, t, J=7.3Hz), 1.65(2H, tq,                       J=7.6Hz, J=7.9Hz), 2.63(3H, s), 2.76(2H, t, J=7.6Hz),                         3.79(3H, s), 3.90(2H, s), 5.37(2H, s), 6.81(1H, d, J=8.6Hz),                  7.06(1H, d, J=7.6Hz), 7.59(1H, d, J=8.9Hz), 7.75(1H, d,                       J=6.9Hz), 7.83(1H, dd, J=7.9Hz, J=7.9Hz), 8.01(1H, dd,                        J=7.9Hz, J=7.9Hz), 8.28(1H, d, J=6.9Hz)                                  50   (solvent:DMSO-d.sub.6) 1.20(3H, t, J=7.6Hz), 2.58(3H, s),                     2.64(2H, q, J=7.6Hz), 3.66(2H, s), 5.38(2H, s), 6.57(1H, s),                  7.06(1H, s), 7.66(1H, d, J=8.6Hz), 7.69(1H, s),                               8.48(1H, dd, J=2.0Hz, J=8.6Hz), 9.22(1H, d, J=2.0Hz),                         12.54(1H, s)                                                             ______________________________________                                    

                                      TABLE 72                                    __________________________________________________________________________    Ex. No.                                                                            Structural formula                                                       __________________________________________________________________________    51                                                                                  ##STR495##                                                              52                                                                                  ##STR496##                                                              53                                                                                  ##STR497##                                                              54                                                                                  ##STR498##                                                              55                                                                                  ##STR499##                                                              __________________________________________________________________________

                  TABLE 73                                                        ______________________________________                                                .sup.1 H-NMR δ ppm                                              ______________________________________                                        51   (solvent: DMSO-d.sub.6) 1.19(3H, t, J=7.6Hz), 2.58(3H, s),                    2.64(2H, q, J=7.6Hz), 4.64(2H, s), 5.45(2H, s), 6.62(1H, s),                  6.93(2H, d, J=8.2Hz), 7.65-7.85(4H, m), 8.05-8.20(2H, m),                     10.35(1H, s), 12.55(1H, s)                                               52   (solvent:DMSO-d.sub.6) 1.20(3H, t, J=7.6Hz), 2.58(3H, s),                     2.64(2H, q, J=7.6Hz), 4.66(2H, s), 5.46(2H, s), 6.62(1H, s),                  6.65-6.75(1H, m), 7.20-7.80(5H, m), 8.05-8.20(2H, m),                         10.41(1H, s) 12.56(1H, s),                                               53   (solvent:DMSO-d.sub.6) 1.21(3H, t, J=7.3Hz), 2.58(3H, s),                     2.65(2H, q, J=7.3Hz), 3.60(2H, s), 3.79(2H, d, J=5.6Hz),                      5.46(2H, s) 6.63(1H, s), 7.09(1H, s), 7.70(1H, s), 7.75-                      7.85(1H, m), 8.1-8.4(3H, m), 12.04(1H, bs), 12.56(1H, s)                 54   (solvent:CDCL.sub.3) 1.31(3H, t, J=7.6Hz), 1.52(2H, d,                        J=6.9Hz), 2.57(3H, s), 2.74(2H, q, J=7.6Hz), 3.71(2H, s),                     4.60(1H, dq, J=7.6Hz, J=7.9Hz), 5.49(2H, s), 6.84(1H, s),                     7.01(1H, d, J=7.3Hz), 7.51(1H, s), 7.63(1H, d, J=7.6Hz),                      7.75(1H, dd, J=7.6Hz, J=8.2Hz), 7.93(1H, dd, J=7.6Hz,                         J=7.6Hz), 8.22(1H, d, J=7.9Hz), 8.33(1H, d, J=8.3Hz)                     55   (solvent:CDCL.sub.3) 1.27(3H, t, J=7.6Hz), 1.43(2H, d,                        J=7.3Hz), 2.59(3H, s), 2.71(2H, q, J=7.3Hz), 3.72(3H, s),                     3.74(2H, s), 4.61(2H, dq, J=6.9Hz, J=7.2Hz), 5.39(2H, s),                     6.49(1H, s), 7.06(1H, d, J=7.6Hz), 7.51(1H, s), 7.72(1H, d,                   J=7.6Hz), 7.76(1H, dd, J=7.2Hz, J=8.4Hz), 8.00(1H, dd,                        J=7.6Hz, J=7.9Hz), 8.27(1H, d, J=7.9Hz), 8.34(1H, d,                          J=8.6Hz)                                                                 ______________________________________                                    

                                      TABLE 74                                    __________________________________________________________________________    Ex. No.                                                                            Structural formula                                                       __________________________________________________________________________    56                                                                                  ##STR500##                                                              57                                                                                  ##STR501##                                                              58                                                                                  ##STR502##                                                              59                                                                                  ##STR503##                                                              60                                                                                  ##STR504##                                                              __________________________________________________________________________

                  TABLE 75                                                        ______________________________________                                                .sup.1 H-NMR δ ppm                                              ______________________________________                                        56   (solvent:CDCL.sub.3) 1.28(3H, t, J=7.4Hz),                                    2.59(3H, s), 2.54(2H, t, J=6.1Hz), 2.70(2H, t, J=7.4Hz),                      3.55(3H, s), 3.56(2H, dd, J=5.9Hz, J=6.3Hz), 3.69(2H, s),                     5.39(2H, s), 6.50(1H, s), 7.06(1H, d, J=7.6Hz), 7.51(1H, s),                  7.73(1H, dd, J=7.9Hz, J=1.0Hz), 7.75(1H, dd, J=7.6Hz,                         J=7.9Hz), 7.99(1H, dd, J=7.6Hz, J=7.9Hz), 8.30(1H, d,                         J=7.9Hz, J=1.0Hz), 8.32(1H, d, J=8.3Hz),                                 57   (solvent:CDCL.sub.3) 1.28(3H, t, J=7.6Hz), 2.60(3H, s),                       2.72(2H, q, J=7.5Hz), 3.76(2H, s), 5.40(2H, s), 6.55(1H, s),                  7.13(1H, d, J=7.3Hz), 7.54(1H, s), 7.76(1H, dd, J=7.3Hz,                      J=7.6Hz), 7.81(1H, d, J=7.6Hz), 8.02(1H, dd, J=7.9Hz,                         J=7.9Hz), 8.25(1H, d, J=7.3Hz), 8.31(1H, d, J=8.2Hz)                     58   (solvent:CDCL.sub.3) 1.31(3H, t, J=7.6Hz), 1.52(2H, d,                        J=6.9Hz), 2.57(3H, s), 2.74(2H, q, J=7.6Hz), 3.71(2H, s),                     4.60(1H, dq, J=7.6Hz, J=7.9Hz), 5.49(2H, s), 6.84(1H, s),                     7.01(1H, d, J=7.3Hz), 7.51(1H, s), 7.63(1H, d, J=7.6Hz),                      7.75(1H, dd, J=7.6Hz, J=8.2Hz), 7.93(1H, dd, J=7.6Hz,                         J=7.6Hz), 8.22(1H, d, J=7.9Hz), 8.33(1H, d, J=8.3Hz)                     59   (solvent:CDCL.sub.3) 1.28(3H, t, J=7.6Hz), 2.58(3H, s),                       2.60(2H, q, J=5.9Hz), 2.71(2H, q, J=7.9Hz), 3.70(2H, s),                      3.60(2H, q, J=5.7Hz), 5.44(1H, s), 6.74(1H, s), 7.03(1H, d,                   J=7.6Hz) 7.50(1H, s), 7.73(1H, d, J=7.3Hz), 7.74(1H, dd,                      J=8.5Hz, J=7.3Hz), 8.00(1H, dd, J=7.9Hz, J=7.6Hz),                            8.25(1H, d, J=7.6Hz), 8.31(1H, d, J=8.2Hz)                               60   (solvent:CDCL.sub.3) 1.29(3H, t, J=7.6Hz), 2.60(3H, s),                       2.73(2H, q, J=7.5Hz), 2.85(1H, dd, J=17.2Hz, J=5.3Hz),                        3.00(1H, dd, J=14.2Hz, J=4.6Hz), 3.76(2H, s), 4.78(1H, t,                     J=5.0Hz), 5.41(2H, s), 6.55(1H, s), 7.13(1H, d, J=7.6Hz),                     7.55(1H, s), 7.74(1H, d, J=7.8Hz), 7.79(1H, dd, J=7.6Hz,                      J=8.2Hz), 8.02(1H, dd, J=7.6Hz, J=7.9Hz), 8.23(1H, d,                         J=6.9Hz), 8.30(1H, d, J=8.6Hz)                                           ______________________________________                                    

                                      TABLE 76                                    __________________________________________________________________________    Ex. No.                                                                            Structural formula                                                       __________________________________________________________________________    61                                                                                  ##STR505##                                                              62                                                                                  ##STR506##                                                              63                                                                                  ##STR507##                                                              64                                                                                  ##STR508##                                                              65                                                                                  ##STR509##                                                              __________________________________________________________________________

                  TABLE 77                                                        ______________________________________                                                .sup.1 H-NMR δ ppm                                              ______________________________________                                        61   (solvent:DMSO-d.sub.6) 1.19(3H, t, J=7.6Hz),                                  2.59(3H, s), 2.64(2H, q, J=7.6Hz), 3.67(2H, s), 5.49(2H, s),                  6.69(1H, s), 7.12(1H, s), 7.71(1H, s), 9.04(1H, s), 9.27(1H, s),              10.06(1H, s), 12.58(1H, br)                                              62   (solvent:CDCL.sub.3) 1.26(3H, t, J=7.6Hz), 1.30(3H, t,                        J=7.3Hz), 2.60 (3H, s), 2.69(2H, q, J=7.6Hz), 3.76(2H, d,                     J=0.7Hz), 4.22(2H, q, J=7.3Hz), 5.33(2H, s), 6.47(1H, s),                     6.94(1H, s), 7.53(1H, s), 9.08 (1H, s), 9.48(1H, s), 10.90(1H,                br), 12.70(1H, s)                                                        63   (solvent:DMSO-d.sub.6) 1.19(3H, t, J=7.6Hz), 2.59(3H, s),                     2.66(2H, q, J=7.6Hz), 2.89(1H, dd, J=8.3Hz, 15.0Hz),                          3.00(1H, dd, J=5.3Hz, 15.0Hz), 3.58(2H, s), 4.4-4.5(1H,                       m), 5.49(2H, s), 6.68(1H, s), 6.94(1H, s), 7.00(1H, s),                       7.71(1H, s), 7.87(1H, s), 8.33(1H, d, J=7.6Hz), 9.05(1H, s),                  9.27(1H, s), 12.60(1H, br)                                               64   (solvent:CDCl.sub.3) 1.20(3H, t, J=7.3Hz), 2.60(3H, s),                       2.70(2H, q, J=7.3Hz), 3.1-3.2(2H, m), 3.72(3H, s),                            3.75(2H, s), 4.8-4.9(1H, m), 5.36(2H, s), 6.48(1H, s),                        6.79(1H, s), 6.91(1H, s), 7.53(1H, s), 7.56(1H, s), 9.10(1H, s),              9.48(1H, s), 12.78(1H, br)                                               65   (solvent:DMSO-d.sub.6) 1.19(3H, t, J=7.6Hz), 2.59(3H, s),                     2.6-2.7(4H, m), 3.61(2H, s), 4.5-4.6(1H, m), 5.49(2H, s),                     6.69(1H, s), 7.08(1H, s), 8.35(1H, d, J=7.6Hz), 9.05(1H, s),                  9.27(1H, s), 12.60(1H, s),                                               ______________________________________                                    

                                      TABLE 78                                    __________________________________________________________________________    Ex. No.                                                                            Structural formula                                                       __________________________________________________________________________    66                                                                                  ##STR510##                                                              67                                                                                  ##STR511##                                                              68                                                                                  ##STR512##                                                              69                                                                                  ##STR513##                                                              70                                                                                  ##STR514##                                                              __________________________________________________________________________

                  TABLE 79                                                        ______________________________________                                                .sup.1 H-NMR δ ppm                                              ______________________________________                                        66   (solvent:CDCl.sub.3) 1.16(3H, t, J=7.6Hz), 1.25(3H, t,                        J=7.6Hz), 1.26(3H, t, J=7.6Hz), 2.59(3H, s), 2.69(2H, q,                      J=7.6Hz), 2.8-3.1(2H, m), 3.71(2H, s), 4.11(2H, q,                            J=7.6Hz), 4.21(2H, q, J=7.6Hz), 4.8-4.9(1H, m),                               5.37(2H, s), 6.47(1H, s), 6.91(1H, s), 7.52(1H, s), 8.03(1H, s),              9.08(1H, s), 9.49(1H, s), 12.68(1H, s),                                  67   (solvent:CDCl.sub.3) 1.27(3H, t, J=7.6Hz), 2.59(3H, t),                       2.70(2H, J=7.6Hz), 3.76(2H, s), 3.78(2H, d, J=0.7Hz),                         5.28(2H, s), 6.43(1H, s), 7.51(1H, s), 6.90(1H, s), 7.72(1H,                  dd, J=7.9, 1.0Hz), 8.00(1H, dd, J=7.9, 7.6Hz), 8.25(1H,                       d, J=7.9Hz)                                                              68   (solvent:CDCl.sub.3) 1.28(3H, t, J=7.4Hz), 2.58(3H, s),                       2.72(2H, q, J=7.5Hz), 3.77(2H, s), 4.05(2H, d, J=5.0Hz),                      5.46(2H, s), 6.89(1H, s), 7.03(1H, d, J=6.6Hz), 7.5(1H, s),                   7.72(1H, d, J=7.9Hz), 7.76(1H, dd, J=7.6, 7.9Hz), 7.99(1H,                    dd, J=7.6, 7.9Hz), 8.24(1H, d, J=7.6Hz), 8.30(1H, d,                          J=8.3Hz)                                                                 69   (solvent:CDCl.sub.3) 1.27(3H, t, J=7.6Hz), 2.59(3H, s),                       2.70(2H, q, J=7.3Hz), 3.72(2H, s), 3.8-4.0(2H, m),                            4.58(3H, t, J=3.8Hz), 5.33 (2H, s), 6.48(1H, s), 6.94(1H, s),                 7.52(1H, s), 7.76(1H, d, J=7.6Hz), 8.03(1H, dd, J=7.9,                        7.9Hz), 8.25(1H, d, J=7.9Hz)                                             70   (solvent:CDCl.sub.3) 1.27(3H, t, J=7.4Hz), 2.60(3H, s),                       2.71(2H, q, J=7.5Hz), 3.37(2H, s), 3.73(3H, s), 3.87(1H, dd,                  J=11.5, 3.3Hz), 3.97(1H, dd, 11.5, 3.3Hz), 4.6-4.7(1H, m),                    5.34(2H, s), 6.48(1H, s), 6.96(1H, s), 7.54(1H, s), 7.77(1H,                  d, J=7.6Hz), 8.04(1H, dd, J=7.9, 7.9Hz), 8.25(1H, d,                          J=7.6Hz)                                                                 ______________________________________                                    

                                      TABLE 80                                    __________________________________________________________________________    Ex. No.                                                                            Structural formula                                                       __________________________________________________________________________    71                                                                                  ##STR515##                                                              72                                                                                  ##STR516##                                                              73                                                                                  ##STR517##                                                              74                                                                                  ##STR518##                                                              75                                                                                  ##STR519##                                                              __________________________________________________________________________

                  TABLE 81                                                        ______________________________________                                                .sup.1 H-NMR δ ppm                                              ______________________________________                                        71   (solvent:CDCl.sub.3) 1.27(3H, t, J=7.6Hz), 1.5-2.2(4H, m),                    2.59(3H, s), 2.70(2H, q, J=7.6Hz), 3.5-3.7(2H, m), 3.85(2H,                   J=2.3Hz), 4.6-4.7(1H, m), 5.32(2H, s), 6.49(1H, s), 6.92(1H,                  s), 7.51(1H, s), 7.73(1H, d, J=7.9Hz), 7.99(1H, dd, J=7.9,                    7.9Hz), 8.23(1H, d, J=7.9Hz)                                             72   (solvent:CDCl.sub.3) 1.26(3H, t, J=7.6Hz), 1.9-2.3(4H, m),                    2.59(3H, s), 2.70(2H, q, J=7.5Hz), 3.6-3.8(2H, m),                            3.82(2H, s), 4.12(2H, q, J=7.2Hz), 4.63(1H, dd, J=8.3,                        3.6Hz), 5.18(2H, d, J=7.9Hz), 5.27(2H, s), 6.44(1H, s),                       6.94(1H, s), 7.35(5H, m), 7.51(1H, s), 7.72(1H, d,                            J=6.9Hz), 8.00(1H, dd, J=7.9, 7.9Hz), 8.25(1H, d,                             J=7.9Hz)                                                                 73   (solvent:CDCl.sub.3) 1.27(3H, t, J=7.6Hz), 2.60(3H, s),                       2.71(2H, q, J=7.3Hz), 2.8-3.1(2H, m), 3.37(2H, d,                             J=5.0Hz), 3.71(2H, s), 4.80(1H, t, J=4.8Hz), 5.35(2H, s),                     6.49(1H, s), 6.93(1H, s), 7.54(1H, s), 7.76(1H, d, J=7.9Hz),                  8.03(1H, dd, J=7.9, 7.9Hz), 8.23(1H, d, J=7.9Hz)                         74   (solvent:CDCl.sub.3) 1.19(3H, t, J=7.1Hz), 1.24(3H, t,                        J=7.4Hz), 1.27(3H, t, J=7.8Hz), 2.59(3H, s), 2.70(2H, q,                      J=7.2Hz), 2.85(1H, dd, J=17.2, 4.6Hz), 3.02(1H, dd,                           J=16.8, 4.6Hz), 3.72(2H, s), 4.10(2H, q, J=7.2Hz),                            4.20(2H, q, J=7.1Hz), 4.85(1H, td, J=4.9, 7.6Hz),                             5.31(2H, s), 6.44(1H, s), 6.89(1H, s), 7.51(1H, s), 7.74(1H, d,               J=7.6Hz), 8.01(1H, dd, J=7.6, 7.9Hz), 8.26(1H, d,                             J=7.6Hz)                                                                 75   (solvent:CDCl.sub.3) 1.27(3H, t, J=7.5Hz), 2.59(3H, s),                       2.69(2H, q, J=7.3Hz), 3.26(2H, d, J=5.0Hz), 3.70(2H, s),                      4.70(1H, t, J=5.0Hz), 5.33(2H, s), 6.48(1H, s), 6.95(1H, s),                  7.05(1H, s), 7.50(1H, s), 7.76(1H, d, J=8.0Hz), 8.00(1H, dd,                  J=8.0, 8.0Hz), 8.22(1H, d, J=8.0Hz)                                      ______________________________________                                    

                                      TABLE 82                                    __________________________________________________________________________    Ex. No.                                                                            Structural formula                                                       __________________________________________________________________________    76                                                                                  ##STR520##                                                              77                                                                                  ##STR521##                                                              78                                                                                  ##STR522##                                                              79                                                                                  ##STR523##                                                              80                                                                                  ##STR524##                                                              __________________________________________________________________________

                  TABLE 83                                                        ______________________________________                                                .sup.1 H-NMR δ ppm                                              ______________________________________                                        76   (solvent:CDCl.sub.3) 1.26(3H, t, J=7.5Hz), 2.59(3H, s),                       2.69(2H, q, J=7.5Hz), 3.15(2H, t, J=4.2Hz), 3.71(3H, s),                      3.73(2H, s), 4.84(1H, dt, J=7.3, 4.2Hz), 5.31(2H, s),                         6.45(1H, s), 6.78(1H, s), 6.88(1H, s), 7.50(1H, s), 7.59(1H, s),              7.72(1H, d, J=7.6Hz), 8.01(1H, dd, J=7.9, 7.9Hz), 8.26(1H,                    d, J=7.6Hz),                                                             77   (solvent:CDCl.sub.3) 1.27(3H, t, J=7.5Hz), 1.9-2.5(4H, m),                    2.0-2.5(4H, m), 2.60(3H, s), 2.71(2H, q, J=7.5Hz),                            3.70(2H, s), 4.56(1H, t, J=4.0Hz), 5.35(2H, s), 6.49(1H, s),                  6.94(1H, s), 7.36(1H, s), 7.77(1H, d, J=7.9Hz), 8.04(1H, dd,                  J=7.6, 7.9Hz), 8.24(1H, d, J=7.6Hz)                                      78   (solvent:CDCl.sub.3) 1.21(3H, t, J=7.1Hz), 1.26(3H, t,                        J=7.4Hz), 1.29(3H, t, J=7.6Hz), 1.9-2.4(4H, m), 2.59(3H,                      s), 2.70(2H, q, J=7.4Hz), 3.70(2H, s), 4.09(2H, q, J=7.2Hz),                  4.19(2H, q, J=6.9Hz), 4.63(1H, td, J=3.7, 7.6Hz), 5.33(2H,                    s), 6.47(1H, s), 6.88(1H, s), 7.51(1H, s), 7.75(1H, d,                        J=6.9Hz), 8.02(1H, dd, J=6.9, 7.6Hz), 8.26(1H, d,                             J=6.9Hz)                                                                 79   (solvent:CDCl.sub.3) 1.21(3H, t, J=7.6Hz), 2.51(3H, s),                       2.62(2H, q, J=7.6Hz), 3.20(2H, br), 4.71(1H, t, J=5.3Hz),                     5.23(2H, s), 6.43(1H, s), 7.41(1H, s), 7.05(1H, s), 7.05(1H, d,               J=7.3Hz), 7.31(1H, s), 7.61(1H, dd, J=7.9Hz), 7.67(1H, dd,                    J=7.9, 7.9Hz), 7.90(1H, dd, J=7.6, 7.6Hz), 8.12(1H, d,                        J=7.3Hz), 8.19(1H, d, J=8.3Hz),                                          80   (solvent:CDCl.sub.3) 1.27(3H, t, J=7.4Hz), 2.59(3H, s),                       2.70(2H, q, J=7.4Hz), 3.17(2H, J=5.0Hz), 3.67(3H, s),                         3.77(2H, s), 4.82(1H, dt, J=6.9, 5.0Hz), 5.22(2H, s), 6.35(1H,                s), 6.71(1H, s), 7.07(1H, d, J=7.3Hz), 7.45(1H, s), 7.51(1H,                  s), 7.67(1H, d, J=7.3Hz), 7.76(1H, dd, J=7.9, 7.9Hz),                         7.98(1H, dd, J=7.9, 7.9Hz), 8.26(1H, d, J=6.9Hz), 8.32(1H,                    d, J=7.9Hz)                                                              ______________________________________                                    

                                      TABLE 84                                    __________________________________________________________________________    Ex. No.                                                                            Structural formula                                                       __________________________________________________________________________    81                                                                                  ##STR525##                                                              82                                                                                  ##STR526##                                                              83                                                                                  ##STR527##                                                              84                                                                                  ##STR528##                                                              85                                                                                  ##STR529##                                                              __________________________________________________________________________

                  TABLE 85                                                        ______________________________________                                                .sup.1 H-NMR δ ppm                                              ______________________________________                                        81   (solvent:CDCl.sub.3) 1.28(3H, t, J=7.4Hz), 1.9-2.5(4H,                        m), 2.60(3H, s), 2.72(2H, q, J=7.4Hz), 3.84(2H, s), 4.5-                      4.6(1H, m), 5.42(2H, s), 6.56(2H, s), 7.26(1H, d, J=7.9Hz),                   7.54(1H, s), 7.76(1H, d, J=8.3Hz, 7.94(1H, dd, J=7.9,                         7.9Hz), 8.03(1H, dd, J=7.9, 7.6Hz), 8.24(1H, d, J=7.9Hz),                     8.39(1H, d, J=8.6Hz)                                                     82   (solvent:CDCl.sub.3) 1.16(3H, t, J=7.3Hz), 1.20(3H, t,                        J=7.1Hz), 1.27(3H, t, J=7.4Hz), 2.59(3H, s),                                  2.71(2H, q, J=7.4Hz), 2.0-2.4(4H, m), 3.74(2H,                                s), 4.03(2H, q, J=7.1Hz), 4.1-4.3(2H, m),                                     4.65(1H, td, J=7.6, 5.3Hz), 5.39(2H, s), 6.49(1H,                             s), 7.06(1H, d, J=6.6Hz), 7.51(1H, s), 7.71(1H, d,                            J=7.3Hz), 7.73(1H, dd, J=7.9, 7.9Hz), 7.99(1H,                                dd, J=7.6, 7.9Hz), 8.27(1H, d, J=7.9Hz),                                      8.34(1H, d, J=7.9Hz)                                                     83   (solvent:CDCl.sub.3) 1.27(3H, t, J=7.4Hz), 2.0-2.1(4H,                        m), 2.58(3H, s), 2.71(2H, q, J=7.4Hz), 3.67(2H,                               m), 3.94(2H, d, J=4.3Hz), 4.75(1H, d, J=5.9Hz),                               5.39(2H, s), 6.56(2H, s), 7.10(1H, d, J=7.6Hz),                               7.50(1H, s), 7.71(1H, d, J=7.9Hz), 7.78(1H, dd,                               J=7.9, 7.9Hz), 7.98(1H, dd, J=7.9, 7.6Hz),                                    8.24(1H, d, J=7.6Hz), 8.37(1H, d, J=8.3Hz)                               84   (solvent:CDCl.sub.3) 1.26(3H, t, J=7.6Hz), 1.9-2.3(4H,                        m), 2.58(3H, s), 2.70(2H, q, J=7.5Hz), 3.6-3.8(2H,                            m), 3.88(2H, s), 4.12(2H, q, J=7.2Hz), 4.63(1H, dd,                           J=8.3, 3.6Hz), 5.17(2H, d, J=7.9Hz), 5.31(2H, s),                             6.47(1H, s), 7.15(1H, d, J=6.6Hz), 7.34(5H, m),                               7.50(1H, s), 7.67(1H, d, J=7.6Hz), 7.68(1H, dd,                               J=7.9, 7.6Hz), 7.97(1H, dd, J=7.9, 7.6Hz),                                    8.26(1H, d, J=6.9Hz), 8.30(1H, d, J=8.3Hz)                               85   (solvent:CDCl.sub.3) 1.28(3H, t, J=7.4Hz), 2.60(3H, s),                       2.72(2H, q, J=7.4Hz), 3.79(2H, s), 3.8-                                       4.1(2H, m), 4.59(1H, t, J=3.5Hz), 5.39(2H,                                    s), 6.52(1H, s), 7.54(1H, s), 7.74(1H, d,                                     J=7.9Hz), 7.80(1H, dd, J=7.6, 8.3Hz), 8.02(1H,                                dd, J=7.9, 7.6Hz), 8.24(1H, d, J=7.9Hz),                                      8.31(1H, d, J=8.2Hz), 7.15(1H, d, J=7.3Hz)                               ______________________________________                                    

                                      TABLE 86                                    __________________________________________________________________________    Ex. No.                                                                            Structural formula                                                       __________________________________________________________________________    86                                                                                  ##STR530##                                                              87                                                                                  ##STR531##                                                              88                                                                                  ##STR532##                                                              89                                                                                  ##STR533##                                                              90                                                                                  ##STR534##                                                              __________________________________________________________________________

                  TABLE 87                                                        ______________________________________                                                .sup.1 H-NMR δ ppm                                              ______________________________________                                        86   (solvent:CDCl.sub.3) 1.27(3H, t, J=7.4Hz), 2.58(3H, s),                       2.69(2H, q, J=7.4Hz), 3.74(3H, s), 3.79(2H, s), 4.00(2H, d,                   J=3.3Hz), 4.71(1H, dt, J=7.3, 3.6Hz), 5.38(2H, s),                            6.50(1H, s), 7.05(1H, d, J=6.6Hz), 7.49(1H, s), 7.70(1H, d,                   J=7.9Hz), 7.75(1H, dd, J=7.6, 8.2Hz), 7.98(1H, dd,                            J=7.9, 6.7Hz), 8.25(1H, d, J=6.6Hz), 8.27(1H, d, J=8.2Hz)                87   (solvent:DMSO-d.sub.6) 1.19(3H, t, J=7.6Hz), 2.60(3H, s),                     2.64(2H, q, J=7.6Hz), 3.53(2H, s), 5.49(2H, s), 6.55(1H, s),                  6.89(1H, s), 7.64(1H, s), 8.04(1H, d, J=5.0Hz), 9.05(1H,                      s)(DMSO-d.sub.6)                                                         88   (solvent:CDCl.sub.3) 1.27(3H, t, J=7.6Hz), 1.29(3H, t,                        J=7.3Hz), 2.58(3H, s), 2.71(2H, q, J=7.6Hz), 3.76(2H,                         s), 4.21(2H, q, J=7.3Hz), 5.43(2H, s), 6.41(1H, s),                           6.94(1H, s), 7.51(1H, s), 8.13(1H, d, J=5.0Hz), 9.09(1H,                      d, J=5.0Hz), 10.93(br), 12.64(1H, s)                                     89   (sovlent:DMSO-d.sub.6) 1.22(3H, t, J=7.6Hz), 2.59(3H, s),                     2.67(2H, q, J=7.6Hz), 3.73(2H, s), 5.56(2H, s), 6.71(1H, s),                  7.20(1H, d, J=7.6Hz), 7.71(1H, s), 7.89(1H, dd, J=7.6Hz,                      7.9Hz), 8.16(1H, d, J=7.9Hz), 9.08(1H, s), 9.32(1H, s),                       10.22(1H, s), 12.58(1H, s)                                               90   (solvent:CDCl.sub.3) 1.27(3H, i, J=7.6Hz), 1.28(3H, t,                        J=7.3Hz), 2.60(3H, s), 2.70(2H, q, J=7.6Hz), 3.80(2H, s),                     4.21(2H, q, J=7.3Hz), 5.38(2H, s), 6.50(1H, s), 7.12(1H, dd,                  J=0.7Hz, 7.6Hz), 7.52(1H, s), 7.78(1H, t, J=7.9Hz),                           8.34(1H, d, J=8.3Hz), 9.04(1H, s), 10.06(1H, s), 12.68(1H,               ______________________________________                                             s)                                                                   

                                      TABLE 88                                    __________________________________________________________________________    Ex. No.                                                                            Structural formula                                                       __________________________________________________________________________    91                                                                                  ##STR535##                                                              92                                                                                  ##STR536##                                                              93                                                                                  ##STR537##                                                              94                                                                                  ##STR538##                                                              95                                                                                  ##STR539##                                                              __________________________________________________________________________

                  TABLE 89                                                        ______________________________________                                                .sup.1 H-NMR δ ppm                                              ______________________________________                                        91   (solvent:CDCl.sub.3) 1.22(3H, t, J=7.6Hz), 2.58(3H, s),                       2.65(2H, q, J=7.6Hz), 3.72(2H, s), 5.20(2H, s), 6.47(1H, s),                  6.87(1H, s), 7.50(1H, s), 7.58(1H, dd, J=7.6, 7.6Hz),                         7.69(1H, d, J=7.6Hz), 7.98(1H, d, J=7.6Hz), 8.09(1H, s)                  92   (solvent:CDCl.sub.3) 1.22(3H, t, J=7.4Hz), 1.28(3H, t,                        J=7.1Hz), 2.58(3H, s), 2.64(2H, q, J=7.4Hz), 3.69(2H, s),                     4.19(2H, q, J=7.1Hz), 5.18(2H, s), 6.45(1H, s), 6.86(1H, s),                  7.47(1H, s), 7.57(1H, dd, J=7.6, 7.6Hz), 7.68(1H, d,                          J=7.6Hz), 7.88(1H, d, J=7.6Hz), 8.02(1H, s)                              93   (solvent:CDCl.sub.3) 1.28(3H, t, J=7.6Hz), 1.47(3H, d,                        J=7.3Hz), 2.60(3H, s), 2.72(2H, q, J=7.6Hz), 3.89(2H, s),                     4.50(1H, dt, J=7.2, 7.3Hz), 5.45(2H, s), 6.57(1H, s), 7.34(1H,                d, J=7.6Hz), 7.53(1H, s), 7.78(1H, d, J=7.9Hz), 8.02(1H,                      dd, J=7.6, 7.9Hz), 8.03(1H, dd, J=7.6, 7.6Hz), 8.23(1H, d,                    J=7.6Hz), 8.45(1H, d, J=8.2Hz),                                          94   (solvent:CDCl.sub.3) 1.27(3H, t, J=7.6Hz), 1.43(3H, d,                        J=7.3Hz), 2.59(3H, s), 2.71(2H, q, J=7.6Hz), 3.72(3H, s),                     3.74(2H, s), 4.61(1H, qd, J=7.1Hz), 5.39(2H, s), 6.49(1H, s),                 7.06(1H, d, J=7.3Hz), 7.51(1H, s), 7.72(1H, d, J=7.3Hz),                      7.76(1H, dd, J=7.9, 7.6Hz), 8.00(1H, dd, J=7.9, 7.6Hz),                       8.27(1H, d, J=8.6Hz), 8.34(1H, d, J=8.3Hz)                               95   (solvent:CDCl.sub.3 /MeoD(4/1)) 1.28(3H, t, J=7.6Hz),                         2.60(3H, s), 2.72(2H, q, J=7.6Hz), 3.77(2H, s), 3.97(2H, s),                  3.99(2H, s), 5.38(2H, s), 6.53(1H, s), 7.14(1H, d, J=7.6Hz),                  7.37(1H, s), 7.75(1H, d, J=7.9Hz), 7.79(1H, dd, J=7.6,                        8.2Hz), 8.02(1H, dd, J=7.6, 7.9Hz), 8.25(1H, d, J=7.9Hz),                     8.30(1H, d, J=8.2Hz)                                                     ______________________________________                                    

                                      TABLE 90                                    __________________________________________________________________________    Ex. No.                                                                            Structural formula                                                       __________________________________________________________________________    96                                                                                  ##STR540##                                                              97                                                                                  ##STR541##                                                              98                                                                                  ##STR542##                                                              99                                                                                  ##STR543##                                                              100                                                                                 ##STR544##                                                              __________________________________________________________________________

                  TABLE 91                                                        ______________________________________                                                .sup.1 H-NMR δ ppm                                              ______________________________________                                        96   (solvent:CDCl.sub.3) 1.21(3H, t, J=7.1Hz), 1.27(3H, t,                        J=7.4Hz), 2.58(3H, s), 2.71(2H, q, J=7.4Hz), 3.78(2H, s),                     4.0-4.1(4H, m), 4.12(2H, q, J=7.1Hz), 5.40(2H, s), 6.52(1H,                   s), 7.07(1H, d, J=7.3Hz), 7.50((1H, s), 7.72(1H, d,                           J=7.9Hz), 7.76(1H, t, J=8.3, 7.6Hz), 7.99(1H, dd,                             J=7.9, 7.9Hz), 8.27(1H, d, J=8.6Hz), 8.30(1H, d,                              J=8.9Hz)                                                                 97   (solvent:DMSO-d.sub.6) 1.30(3H, t, J=7.6Hz),                                  2.59(3H, s), 2.72(2H, q, J=7.6Hz), 3.49(1H, s), 4.13(2H,                      s), 5.40(2H, s), 6.48(1H, s), 7.17(1H, dd, J=1.8Hz, 7.9Hz),                   7.51(1H, s), 7.61(1H, dd, J=7.9Hz, 8.3Hz), 7.76(1H, d,                        J=7.9Hz), 8.02(1H, dd, J=7.9Hz, 7.9Hz), 8.26(1H, d,                           J=8.6Hz), 8.75(1H, dd, J=1.8Hz, 8.3Hz), 12.18(1H, br),                        12.63(1H, s),                                                            98   (solvent:CDCl.sub.3) 1.27(3H, t, J=7.6Hz), 1.31(1H, t,                        J=7.1Hz), 2.58(3H, s), 2.70(2H, q, J=7.6Hz), 3.99(2H, s),                     4.26(2H, q, J=7.1Hz), 5.35(2H, s), 6.46(1H, s), 7.11(1H, dd,                  J=1.7Hz, 7.9Hz), 7.36(1H, dd, J=7.9Hz, 7.9Hz), 7.49(1H,                       s), 7.72(1H, dd, J=1.0Hz, 7.9Hz), 7.98(1H, dd, J=7.9Hz,                       7.9Hz), 8.23(1H, dd, J= 1.0Hz, 7.9Hz), 8.63(1H, dd,                           J=2.0Hz), 8.6Hz), 12.29(1H, br), 12.62(1H, s)                            99   (solvent:CDCl.sub.3) 1.29(3H, t, J=7.4Hz), 2.57(3H, s),                       2.72(2H, t, J=7.4Hz), 2.96(1H, dd, J=17.0, 4.5Hz),                            3.09(1H, dd, J=17.0, 4.5Hz), 3.77(2H, s), 4.85(1H, br),                       5.49(2H, d, J=3.3Hz), 6.72(1H, s), 7.02(1H, d, J=8.3Hz),                      7.49(1H, s), 7.65(1H, d, J=7.9Hz), 7.75(1H, dd, J=7.6,                        8.3Hz), 7.94(1H, dd, J=7.6, 8.3Hz), 7.94(1H, dd, J=7.9,                       7.6Hz), 8.19(1H, d, J=7.6Hz), 8.32(1H, d, J=8.3Hz)                       100  (solvent:CDCl.sub.3) 1.10(3H, t, J=7.0Hz), 1.17(3H, t,                        J=7.1Hz), 1.28(3H, t, J=7.4Hz), 2.59(3H, s), 2.71(2H, q,                      J=7.4Hz), 2.85(1H, dd, J=17.0, 4.6Hz), 3.02(1H, dd,                           J=17.0, 4.6Hz), 3.75(2H, s), 4.00(2H, q, J=7.1Hz),                            4.16(2H, q, J=7.0Hz), 4.85(1H, dt, J=7.6, 4.6Hz), 5.39(2H,                    s), 6.49(1H, s), 7.05(1H, d, J=7.3Hs), 7.51(1H, s), 7.72(1H,                  d, J=7.6Hz), 7.73(1H, dd, J=7.3, 7.6Hz), 7.99(1H, dd,                         J=7.6, 7.9Hz), 8.27(1H, d, J=7.3Hz), 8.34(1H, d,                              J=8.3Hz)                                                                 ______________________________________                                    

                                      TABLE 92                                    __________________________________________________________________________    Ex. No.                                                                            Structural formula                                                       __________________________________________________________________________    101                                                                                 ##STR545##                                                              102                                                                                 ##STR546##                                                              103                                                                                 ##STR547##                                                              104                                                                                 ##STR548##                                                              105                                                                                 ##STR549##                                                              __________________________________________________________________________

                  TABLE 93                                                        ______________________________________                                                .sup.1 H-NMR δ ppm                                              ______________________________________                                        101  (solvent:DMSO-d.sub.6) 1.17(3H, t, J=7.6Hz),                                  2.56(3H, s), 2.59(1H, m), 2.69(1H, m), 3.59(2H, s), 3.6-                      4.3(2H, br), 4.56(1H, m), 5.29(2H, s), 6.60(1H, s), 6.96(1H,                  s), 6.96(1H, s), 7.56(1H, t, J=7.9Hz), 7.64(1H, s), 7.68(1H,                  d, J=7.9Hz), 8.07(1H, d, J=7.9Hz), 8.19(1H, s), 8.23(1H, d,                   J=7.6Hz), 12.6(1H, s)                                                    102  (solvent:CDCl.sub.3 /DMSO-d.sub.6 (10/1)) 1.15-1.31(9H, m),                   2.57(3H, s), 2.64(2H, q, J=7.3Hz), 2.84(1H, dd, J=17.2,                       4.6Hz), 3.03(1H, dd, J=17.2, 4.3Hz), 3.67(2H, s), 4.15-                       4.27(4H, m), 4.85(1H, ddd, J=7.9, 4.6, 4.3Hz), 5.19(1H, s),                   6.46(1H, s), 6.78(1H, s), 7.48(1H, s), 7.57(1H, t, J=7.9Hz),                  7.69(1H, d, J=7.9Hz), 7.94(1H, brd, J=8.3Hz), 7.97(1H,                        d, J=7.9Hz), 8.10(1H, s), 12.68(1H, s)                                   103  (solvent:DMSOO-d.sub.6) 1.21(3H, t, J=7.3Hz), 2.58(H, s),                     2.6-2.7(4H, m), 4.08(1H, s), 4.60(1H, m), 5.46(2H, s),                        5.6-6.4(2H, br), 6.62(1H, s), 7.68(1H, s), 7.80(2H, d),                       8.15(2H, m), 8.78(1H, d, J=7.9Hz), 12.55(1H, s)                          104  (solvent:CDCl.sub.3) 1.23-1.65(9H, m), 2.59(3H, s),                           2.70(2H, q, J=7.3Hz), 2.85(1H, dd, J=17.2, 4.6Hz),                            3.05(1H, dd, J=17.2, 4.6Hz), 4.10(2H, s), 4.15(2H, q,                         J=7.3Hz), 4.22(2H, q, J=7.3Hz), 4.87(1H, dt, J=7.9,                           4.6Hz), 5.32(1H, s), 6.45(1H, s), 7.24(1H, brd), 7.52(1H, s),                 7.75(1H, d, J=7.3Hz), 8.01(1H, t, J=7.9Hz), 8.26(1H, d,                       J=7.9Hz), 12.67(1H, s)                                                   105  (solvent:DMSO-d.sub.6) 0.96(6H, m), 1.30(3H, t, J=7.6Hz),                     2.17(1H, m), 2.58(3H, s), 2.73(2H, q, J=7.6Hz), 3.75(2H,                      m), 4.67(1H, m), 5.42(2H, s), 6.83(1H, s), 7.02(1H, d,                        J=7.9Hz), 7.51(1H, s), 7.65(1H, d, J=7.9Hz), 7.75(1H,                         t, J=7.9Hz), 7.95(1H, t, J=7.9Hz), 8.22(1H, d,                                J=7.9Hz), 8.32(1H, d, J=7.9Hz), 8.91(1H, brd),                                10.87(1H, s)                                                             ______________________________________                                    

                                      TABLE 94                                    __________________________________________________________________________    Ex. No.                                                                            Structural formula                                                       __________________________________________________________________________    106                                                                                 ##STR550##                                                              107                                                                                 ##STR551##                                                              108                                                                                 ##STR552##                                                              109                                                                                 ##STR553##                                                              110                                                                                 ##STR554##                                                              __________________________________________________________________________

                  TABLE 95                                                        ______________________________________                                                .sup.1 H-NMR δ ppm                                              ______________________________________                                        106  (solvent:CDCl.sub.3) 0.91(3H, m), 1.27(3H, t,                                 J=7.3Hz), 2.18(1H, m), 2.59(3H, s), 2.71(2H, q, J=7.3Hz),                     3.71(3H, s), 3.76(2H, s), 4.60(1H, s), 5.34(2H, s), 6.46(1H,                  s), 7.05(1H, d, J=7.6Hz), 7.51(1H, s), 7.73(1H, t, J=                         7.6Hz), 7.78(1H, d, J=7.9Hz), 7.97(1H, br), 8.00(1H, t,                       J=7.9Hz), 8.27(1H, d, J=7.9Hz), 8.35(1H, d, J=7.9Hz),                         10.54(1H, s), 12.62(1H, s)                                               107  (solvent:DMSO-d.sub.6) 1.31(3H, t, J=7.6Hz), 2.01(3H,                         s), 2.15(1H, m), 2.35(1H, m), 2.55(2H, m), 2.58(3H, s),                       2.74(2H, q, J=7.6Hz), 3.80(1H, d, J=15.8Hz), 3.68(1H,                         d, J=15.8Hz), 4.73(1H, m), 5.48(2H, s), 6.83(1H, s),                          7.02(1H, d, J=7.6Hz), 7.51(1H, s), 7.63(1H, d, J=7.6Hz),                      7.75(1H, t, J=7.6Hz), 7.94(1H, t, J=7.6Hz), 8.22(1H, d,                       J=7.6Hz), 8.33(1H, d, J=7.6Hz), 9.08(1H, brd),                                10.87(1H, s)                                                             108  (solvent:CDCl.sub.3) 1.1-1.3(6H, m), 2.00(3H, s),                             2.05-2.2(2H, m), 2.47(2H, m), 2.59(3H, s), 2.70(2H, q,                        J=7.3Hz), 3.74(2H, s), 4.16(2H, m), 4.71(1H, m), 5.40(2H,                     s), 6.50(1H, s), 7.06(1H, d, J=7.6Hz), 7.51(1H, s),                           7.75(1H, t, J=7.6Hz), 7.77(1H, d, J=7.9Hz), 7.96(1H,                          br), 8.00(1H, t, J=7.6Hz), 8.27(1H, d, J=7.3Hz),                              8.34(1H, d, J=8.3Hz), 10.53(1H, s), 12.63(1H, s)                         109  (solvent:DMSO-d.sub.6) 1.21(3H, t, J=7.3Hz), 2.51(3H,                         s), 2.63(4H, m), 3.89(2H, s), 4.59(1H, m), 5.42(2H, s),                       6.63(1H, s), 7.29(1H, d, J=8.3Hz), 7.44(1H, t, J=                             8.3Hz), 7.65(1H, s), 7.83(1H, d, J=7.3Hz), 8.18(1H, t,                        J=7.3Hz), 8.23(1H, brd), 8.47(1H, d, J=8.3Hz),                                8.59(1H, d, J=7.3Hz), 12.16(1H, s), 12.51(1H, s),                             12.6(2H, br)                                                             110  (solvent:CDCl.sub.3) 1.15(3H, t, J=7.3Hz), 1.17(3H, t,                        J=7.3Hz), 1.27(3H, t, J=7.3Hz), 2.59(3H, s), 2.71(1H, q,                      J=7.3Hz), 2.83(1H, dd, J=16.8Hz, 5.3Hz), 2.94(1H, dd,                         J=16.8Hz, 5.3Hz), 3.96(1H, d, J=13.5Hz), 4.07(1H, d,                          J=13.5Hz), 4.11(2H, q, J=7.3Hz), 4.12(2H, q, J=7.3Hz),                        4.81(1H, dt, J=8.2Hz, 5.3Hz), 5.39(2H, s), 6.48(1H, s),                       7.18(1H, dd, J=7.9Hz, 1.7Hz), 7.41(1H, t, J=7.9Hz),                           7.50(1H, s), 7.76(1H, d, J=7.9Hz), 8.01(1H, t, J=7.9Hz),                      8.25(1H, d, J=7.9Hz), 8.63(1H, dd, J=7.4Hz, 1.7Hz),                           8.69(1H, d, J=8.2Hz), 12.32(1H, s), 12.61(1H, s)                         ______________________________________                                    

                                      TABLE 96                                    __________________________________________________________________________    Ex. No.                                                                            Structural formula                                                       __________________________________________________________________________    111                                                                                 ##STR555##                                                              112                                                                                 ##STR556##                                                              113                                                                                 ##STR557##                                                              114                                                                                 ##STR558##                                                              115                                                                                 ##STR559##                                                              __________________________________________________________________________

                  TABLE 97                                                        ______________________________________                                        .sup.1 H-NMR δ ppm                                                      ______________________________________                                        111  (solvent:DMSO-d.sub.6) 1.12(3H, d, J=6.6Hz), 1.22(3H, t, J=                   7.6Hz), 2.30(1H, dd, J=15.2Hz, 7.3Hz), 2.46(1H, dd, J=                        15.2Hz, 7.3Hz), 2.58(3H, s), 2.67(2H, q, J=7.6Hz), 3.56(2H,                   s), 4.10(1H, m), 5.47(2H, s), 6.64(2H, s), 7.13(1H, d, J=                     7.6Hz), 7.69(1H, s), 7.80-7.86(2H, m), 8.10-8.30(4H, m),                      10.35(1H, s), 12.17(1H, s), 12.56(1H, s)                                 112  (solvent:CDCl.sub.3) 1.26(6H, m), 2.53(2H, d, J=5.3Hz), 2.59                  (3H, s), 2.71(3H, s), 2.71(2H, m), 3.55(3H, s), 3.68(2H, s),                  4.36(1H, m), 5.36(2H, s), 6.47(1H, s), 7.06(1H, d, J=7.6Hz),                  7.42(1H, brd, J=7.9Hz), 7.51(1H, s), 7.70(1H, d, J=7.6Hz),                    7.75(1H, t, J=7.6Hz), 7.99(1H, t, J=7.6Hz), 8.27(1H, d, J=                    7.6Hz), 8.31(1H, d, J=7.6Hz), 10.48(1H, s), 12.65(1H, s)                 113  (solvent:DMSO-d.sub.6) 1.23(3H, t, J=7.3Hz), 2.14(1H, m), 2.6                 (1H, m), 2.58(3H, s), 2.67(2H, q, J=7.3Hz), 3.45-3.70(2H,                     m), 3.83(1H, m), 4.22(1H, m), 5.02(0.4H, m), 4.57(0.6H, m),                   5.48(2H, s), 6.65(1H, s), 7.14(1H, m), 7.69(1H, s), 7.65-7.90                 (2H, m), 8.15-8.30(3H, m), 10.32(0.6H, s), 10.34(0.4H, s),                    12.55(1H, s), 12.90(1H, br)                                              114  (solvent:CDCl.sub.3) 1.27(3H, t, J=7.6Hz), 2.20-2.40(1H, m),                  2.5-2.7(1H, m), 2.59(3H, s), 2.71(2H, q, J=7.6Hz), 3.64                       (0.4H, s), 3.68(0.6H, s), 3.77(0.6H, s), 3.80(0.4H, s), 4.05-4.40             (2H, m), 4.79(0.6H, m), 4.95(0.4H, m), 5.34(2H, s), 6.48(1H,                  s), 7.13(0.4H, d, J=7.6Hz), 7.19(0.6H, d, J=7.6Hz), 7.51                      (1H, s), 7.70(1H, d, J=7.6Hz), 7.75(1H, m), 7.98(1H, t, J=                    7.6Hz), 8.27(1H, d, J=7.6Hz), 8.32(1H, d, J=7.6Hz), 10.34                     (1H, s), 12.67(1H, s)                                                    115  (solvent:CDCl.sub.3) 1.28(3H, t, J=7.6Hz), 2.58(3H, s), 2.72(2H,              q, J=7.6Hz), 2.91(2H, t, J=5.7Hz), 3.87(2H, s), 3.92(2H, t,                   J=5.7Hz), 5.46(2H, s), 6.60(1H, s), 6.88(1H, d, J=7.3Hz),                     7.12(1H, d, J=6.6Hz), 7.50(1H, s), 7.62(1H, dd, J=7.6,                        8.3Hz), 7.73(1H, d, J=7.9Hz), 7.78(1H, dd, J=7.6, 8.3Hz),                     7.98(1H, dd, J=7.6, 7.9Hz), 8.06(1H, d, J=8.3Hz), 8.27(1H,                    d, J=7.9Hz), 8.40(1H, d, J=7.6Hz)                                        ______________________________________                                    

                                      TABLE 98                                    __________________________________________________________________________    Ex. No.                                                                            Structural formula                                                       __________________________________________________________________________    116                                                                                 ##STR560##                                                              117                                                                                 ##STR561##                                                              118                                                                                 ##STR562##                                                              119                                                                                 ##STR563##                                                              120                                                                                 ##STR564##                                                              __________________________________________________________________________

                  TABLE 99                                                        ______________________________________                                        .sup.1 H-NMR δ ppm                                                      ______________________________________                                        116  (solvent:CDCl.sub.3 /MeODC(1/4))1.28(3H, t, J=7.6Hz), 2.60                    (3H, s), 2.72(2H, q, J=7.6Hz), 2.88(2H, t, J=6.3Hz), 3.86                     (2H, t, J=6.3Hz), 3.97(2H, s), 5.39(2H, s), 6.52(1H, s), 6.68                 (1H, s), 7.19(1H, d, J=7.6Hz), 7.55(1H, s), 7.76(1H, d, J=                    7.9Hz), 7.83(1H, dd, J=8.2, 7.6Hz), 8.05(1H, dd, J=7.6, J=                    7.9Hz), 8.25(1H, d, J=7.6Hz), 8.33(1H, d, J=8.2Hz)                       117  (solvent:CDCl.sub.3) 1.0-1.3(5H, m), 2.59(3H, s), 2.71(2H, q,                 J=7.5Hz), 3.4-3.9(6H, m), 3.4-3.9(6H, m), 3.93(2H, s),                        5.35(2H, s), 6.49(1H, s), 7.0-7.2(1H, m), 7.51(1H, s),                        7.6-8.4(5H, m)                                                           118  (solvent:CDCl.sub.3) 1.27(3H, t, J=7.4Hz), 2.58(3H, s), 2.70(2H,              q, J=7.4Hz), 3.6-4.0(8H, m), 4.00(2H, s), 5.35(2H, s),                        6.51(1H, s), 7.11(1H, d, J=7.6Hz), 7.50(1H, s),                               7.70(1H, d, J=7.6Hz), 7.76(1H, dd, J=7.6, 7.6Hz),                             7.97(1H, dd, J=7.6, 7.9Hz), 8.24(1H, d, J=7.9Hz),                             8.32(1H, d, J=7.6Hz)                                                     119  (solvent:CDCl.sub.3) 1.28(3H, t, J=7.4Hz), 2.60(3H, s), 2.71(2H,              q, J=7.4Hz), 3.42(2H, t, J=6.6Hz), 3.68(2H, t, J=6.6Hz),                      3.71(2H, s), 5.37(2H, s), 6.50(1H, s), 7.13(1H, d, J=7.6Hz),                  7.53(1H, s), 7.74(1H, d, J=7.6Hz), 7.76(1H, dd, J=8.2,                        7.6Hz), 8.02(1H, dd, J=7.6, 7.6Hz), 8.25(1H, d, J=7.6Hz),                     8.27(1H, d, J=8.2Hz)                                                     120  (solvent:CDCl.sub.3) 1.27(3H, t, J=7.4Hz), 2.59(3H, s), 2.71(2H,              q, J=7.4Hz), 2.93(2H, t, J=6.8Hz), 4.48(2H, t, J=6.8Hz),                      5.32(2H, s), 6.31(1H, d, J=8.1Hz), 6.45(1H, d, J=8.1Hz),                      7.03(1H, d, J=7.6Hz), 7.29(1H, d, J=8.1, 8.1Hz), 7.69(1H,                     d, J=7.6Hz) 7.71(1H, dd, J=7.6, 7.6Hz), 7.97(1H, dd, J=                       7.6, 7.6Hz), 8.26(1H, d, J=7.6Hz), 8.33(1H, d, J=7.6Hz)                  ______________________________________                                    

                                      TABLE 100                                   __________________________________________________________________________    Ex. No.                                                                            Structural formula                                                       __________________________________________________________________________    121                                                                                 ##STR565##                                                              122                                                                                 ##STR566##                                                              123                                                                                 ##STR567##                                                              124                                                                                 ##STR568##                                                              125                                                                                 ##STR569##                                                              __________________________________________________________________________

                  TABLE 101                                                       ______________________________________                                        .sup.1 H-NMR δ ppm                                                      ______________________________________                                        121  (solvent:CDCl.sub.3) 1.28(3H, t, J=7.4Hz), 2.59(3H, s), 2.71(2H,              q, J=7.4Hz), 2.96(2H, t, J=5.5Hz), 3.96(2H, t, J=5.5Hz),                      5.33(2H, s), 6.45(1H, s), 6.73(1H, s), 7.51(1H, s),                           7.72(1H, d, J=6.9Hz), 8.00(1H, dd, J=7.9, 7.6Hz),                             8.25(1H, dd, J=7.6Hz)                                                    122  (solvent:DMSO-d.sub.6) 0.41(3H, t, J=7.6Hz), 1.30(3H, t, J=                   7.6Hz), 1.7-1.9(2H, m), 2.57(3H, s), 3.74(2H, ABq, J=                         15.4Hz, 5.5Hz), 4.66(1H, m), 5.46(2H, s), 6.83(1H, s), 7.02                   (1H, d, J=7.6Hz), 7.51(1H, s), 7.63(1H, d, J=7.6Hz), 7.75                     (1H, t, J=7.6Hz), 7.94(1H, t, J=7.6Hz), 8.22(1H, d, J=                        7.6Hz), 8.32(1H, d, J=7.6Hz), 8.94(1H, m), 10.86(1H, s)                  123  (solvent:CDCl.sub.3) 0.88(3H, t, J=7.3Hz), 1.27(3H, t, J=                     7.6Hz), 1.7-1.9(2H, m), 2.59(3H, s), 2.71(2H, q, J=7.6Hz),                    3.71(3H, s), 3.74(2H, s), 4.63(1H, m), 5.37(2H, s), 6.47(1H,                  s), 7.06(1H, d, J=7.6Hz), 7.71(1H, d, J=7.6Hz), 7.75(1H, t,                   J=7.6Hz), 7.86(1H, m), 8.00(1H, t, J=7.6Hz), 8.27(1H, d,                      J=7.6Hz), 8.35(1H, m, J=7.6Hz), 10.53(1H, s), 12.63(1H, s)               124  (solvent:DMSO-d.sub.6) 1.19(3H, t, J=7.6Hz), 2.59(3H, s),                     2.65(2H, q, J=7.6Hz), 3.89(2H, s), 5.53(2H, s), 6.73(1H, s),                  7.37(1H, d, J=7.9Hz), 7.51(1H, t, J=7.9Hz), 7.69(1H, s),                      8.46(1H, d, J=7.9Hz), 9.13(1H, s), 9.37(1H, s), 11.96(1H, s),                 12.50(1H, br), 12.54(1H, s)                                              125  (solvent:CDCl.sub.3) 1.26(3H, t, J=7.6Hz), 1.31(3H, t, J=                     7.3Hz), 2.60(3H, s), 2.69(2H, q, J=7.6Hz), 3.98(3H, s),                       4.25(2H, q, J=7.3Hz), 5.39(2H, s), 6.47(1H, s), 7.15(1H, dd,                  J=8.3Hz, 2.0Hz), 7.39(1H, t, J=8.3Hz), 7.52(1H, s),                           8.61(1H, dd, J=8.3Hz, 2.0Hz), 9.07(1H, s), 9.46(1H, s),                       12.12(1H, s), 12.65(1H, s)                                               ______________________________________                                    

                                      TABLE 102                                   __________________________________________________________________________    Ex. No.                                                                            Structural formula                                                       __________________________________________________________________________    126                                                                                 ##STR570##                                                              127                                                                                 ##STR571##                                                              128                                                                                 ##STR572##                                                              129                                                                                 ##STR573##                                                              130                                                                                 ##STR574##                                                              __________________________________________________________________________

                  TABLE 103                                                       ______________________________________                                        .sup.1 H-NMR δ ppm                                                      ______________________________________                                        126  (solvent:CDCl.sub.3) 1.28(3H, t, J=7.4Hz), 2.58(3H, s), 2.71(2H,              q, J=7.4Hz), 3.02(2H, t, J=5.5Hz), 4.05(2H, t, J=5.5Hz),                      5.34(2H, s), 6.49(1H, s), 6.98(1H, d, J=7.6Hz), 7.50(1H, s),                  7.70(1H, d, J=7.9Hz), 7.72(1H, dd, J=7.9, 7.9Hz), 7.98(1H,                    d, J=7.9, 7.6Hz), 8.27(1H, d, J=7.6Hz), 8.30(1H, d,                           J=8.2Hz)                                                                 127  (solvent:CDCl.sub.3) 1.10(3H, t, J=7.1Hz), 1.17(3H, t, J=                     7.3Hz), 1.27(3H, t, J=8.1Hz), 2.59(3H, s), 2.71(2H, q, J=                     7.2Hz), 2.84(1H, dd, J=16.8, 4.6Hz), 3.02(1H, dd, J=16.8,                     4.3Hz), 3.75(2H, s), 4.00(2H, q, J=7.1Hz), 4.16(2H, q, J=                     7.0Hz), 4.85(1H, dt, J=7.9, 4.6Hz), 5.39(2H, s), 6.49(1H, s),                 7.05(1H, dd, J=7.6, 0.6Hz), 7.51(1H, s), 7.72(1H, d, J=                       7.6Hz), 7.75(1H, dd, J=7.9, 7.9Hz), 7.99(1H, dd, J=7.6,                       7.9Hz), 8.26(1H, dd, J=8.6, 1.0Hz), 8.34(1H, dd, J=8.2,                       0.7Hz)                                                                   128  (solvent:DMSO-d.sub.6) 0.90(3H, d, J=7.6Hz), 0.91(3H, d, J=                   7.6Hz), 1.19(3H, t, J=7.3Hz), 2.07(1H, m), 2.58(3H, s),                       2.65(2H, q, J=7.3Hz) 3.92(2H, ABq, J=21.8, 15.5Hz), 4.18                      (1H, dd, J=8.3, 5.6Hz), 5.42(2H, s), 6.62(1H, s), 7.29                        (1H, dd, J=8.3, 2.0Hz), 7.48(1H, t, J=8.3Hz), 7.68(1H, s),                    7.85(1H, m), 8.20(2H, m), 8.45(1H, dd, J=8.3, 2.0Hz), 8.46                    (1H, d, J=8.3Hz), 12.17(1H, s), 12.51(1H, s), 12.60(1H, s)               129  (solvent:CDCl.sub.3) 0.88(3H, t, J=7.3Hz), 0.89(3H, t, J=                     7.3Hz), 1.27(3H, t, J=7.6Hz), 2.18(1H, m), 2.59(3H, s), 2.71                  (2H, q, J=7.6Hz) 3.65(3H, s), 4.04(2H, Abq, J=17.5,                           13.2Hz), 4.40(1H, m), 5.36(2H, s) 6.45(1H, s), 7.18(1H, dd,                   J=8.3, 2.0Hz), 7.41(1H, t, J=8.3Hz), 7.51(1H, s), 7.74                        (1H, d, J=7.9Hz), 8.00(1H, t, J=7.9Hz), 8.25(1H, d, J=                        7.9Hz), 8.63(1H, dd, J=8.3, 2.0Hz), 8.78(1H, d, J=8.6Hz),                     12.38(1H, s), 12.62(1H, s)                                               130  (solvent:DMSO-d.sub.6) 1.10(3H, d, J=7.3Hz), 1.22(3H, t, J=                   7.6Hz), 2.58(3H, s), 2.67(2H, q, J=7.6Hz), 3.76(2H, ABq,                      J=20.5, 14.9Hz), 4.17(1H, br), 4.26(1H, m), 4.95(1H, m),                      5.47(2H, s), 6.63(1H, s), 7.20(1H, d, J=7.6Hz), 7.69(1H, s),                  7.82(2H, m), 8.18(4H, m), 10.36(1H, s), 12.50(1H, br), 12.55                  (1H, s)                                                                  ______________________________________                                    

                                      TABLE 104                                   __________________________________________________________________________    Ex. No.                                                                            Structural formula                                                       __________________________________________________________________________    131                                                                                 ##STR575##                                                              132                                                                                 ##STR576##                                                              133                                                                                 ##STR577##                                                              134                                                                                 ##STR578##                                                              135                                                                                 ##STR579##                                                              __________________________________________________________________________

                  TABLE 105                                                       ______________________________________                                        .sup.1 H-NMR δ ppm                                                      ______________________________________                                        131  (solvent:CDCl.sub.3) 1.16(3H, d, J=7.3Hz), 1.26(3H, t, J=                     7.6Hz), 2.57(3H, s), 2.69(2H, q, J=7.6Hz), 3.01(1H, br), 3.69                 (3H, s), 4.05(2H, ABq, J=20.1Hz, 13.9Hz), 4.50(1H, m),                        4.54(1H, m), 5.36(2H, s), 6.49(1H, s), 7.20(1H, dd, J=8.3Hz,                  1.7Hz), 7.41(1H, t, J=8.3Hz), 7.48(1H, s), 7.72(1H, d, J=                     7.9Hz), 7.98(1H, t, J=7.9Hz), 8.21(1H, d, J=7.9Hz), 8.51                      (1H, d, J=8.6Hz), 8.60(1H, dd, J=8.3, 1.7Hz), 12.34(1H, s),                   12.64(1H, s)                                                             132  (solvent:DMSO-d.sub.6) 1.19(3H, t, J=7.3Hz), 1.31(3H, d, J=                   7.3Hz), 2.58(3H, s), 2.64(2H, q, J=7.6Hz), 3.85(2H, m), 4.24                  (1H, m), 5.43(2H, s), 6.63(1H, s), 7.31(1H, dd, J=8.3,                        1.7Hz), 7.47(1H, t, J=8.3Hz), 7.68(1H, s), 7.85(1H, m), 8.21                  (2H, m), 8.46(1H, dd, J=8.3, 1.7Hz), 8.54(1H, d, J=7.9Hz),                    12.15(1H, s), 12.50(1H, s), 12.55(1H, br)                                133  (solvent:DMSO-d.sub.6) 0.92(3H, t, J=7.6Hz), 1.20(3H, t, J=                   7.6Hz), 1.6-1.9(1H, m), 2.58(3H, s), 2.65(2H, q, J=7.6Hz),                    3.89(2H, ABq, J=20.8, 15.8Hz), 4.17(1H, m), 5.42(2H, s),                      6.63(1H, s), 7.30(1H, dd, J=8.3Hz, 2.0Hz), 7.47(1H, t, J=                     8.3Hz), 7.68(1H, s), 7.85(2H, m), 8.21(2H, m), 8.45(1H, dd,                   J=8.3, 2.0Hz), 8.50(1H, d, J=7.9Hz), 12.16(1H, s), 12.50                      (1H, s), 12.55(1H, br)                                                   134  (solvent:CDCl.sub.3) 0.89(3H, t, J=7.3Hz), 1.27(3H, t, J=                     7.6Hz), 1.70-1.85(2H, m), 2.59(3H, s), 2.71(2H, q, J=7.6Hz),                  3.66(3H, s), 4.02(2H, ABq, J=18.8, 13.2Hz), 4.45(1H, m),                      5.38(2H, s), 6.48(1H, s), 7.18(1H, dd, J=7.9, 2.0Hz), 7.41                    (1H, t, J=7.9Hz), 7.50(1H, s), 7.75(1H, d, J=7.9Hz), 8.00                     (1H, t, J=7.9Hz), 8.25(1H, d, J=7.9Hz), 8.61(1H, brd), 8.63                   (1H, dd, J=7.9Hz, 2.0Hz), 12.33(1H, s), 12.63(1H, s)                     135  (solvent:DMSO-d.sub.6) 1.20(3H, t, J=7.6Hz), 2.58(3H, s), 2.65                (2H, q, J=7.6Hz), 2.7-2.9(2H, m), 3.87(2H, s), 4.58(1H, m),                   5.43(2H, s), 6.64(1H, s), 7.30(1H, dd, J=8.3, 2.0Hz),                         7.47(1H, t, J=8.3Hz), 7.68(1H, s), 7.84(1H, m), 8.21(1H, m),                  8.46(1H, dd, J=8.3Hz, 2.0Hz), 8.61(1H, d, J=7.9Hz), 12.14                     (1H, s), 12.51(1H, s), 12.55(2H, br)                                     ______________________________________                                    

                                      TABLE 106                                   __________________________________________________________________________    Ex. No.                                                                            Structural formula                                                       __________________________________________________________________________    136                                                                                 ##STR580##                                                              137                                                                                 ##STR581##                                                              138                                                                                 ##STR582##                                                              139                                                                                 ##STR583##                                                              140                                                                                 ##STR584##                                                              __________________________________________________________________________

                  TABLE 107                                                       ______________________________________                                        .sup.1 H-NMR δ ppm                                                      ______________________________________                                        136  (solvent: CDCl.sub.3) 1.15(3H, t, J=7.3Hz), 1.17(3H, t, J=                    7.3Hz), 1.27(3H, t, J=7.6Hz), 2.59(3H, s), 2.71(2H, q, J=                     7.6Hz), 2.80-2.95(2H, m), 3.93-4.16(6H, m), 4.81(1H, m),                      5.39(2H, s), 6.47(1H, s), 7.18(1H, d, J=8.3Hz), 7.41(1H, t,                   J=8.3Hz), 7.51(1H, s), 7.76(1H, d, J=7.9Hz), 8.01(1H, t,                      J=7.9Hz), 8.25(1H, d, J=7.9Hz), 8.62(1H, dd, J=8.3,                           1.7Hz), 8.69(1H, d, J=7.9Hz), 12.31(1H, s), 12.61(1H, s)                 137  (solvent:DMSO-d.sub.6) 1.09(3H, d, J=7.6Hz), 1.20(3H, t, J=                   7.6Hz), 2.58(3H, s), 2.66(2H, q, J=7.6Hz), 3.96(2H, ABq,                      J=20.8, 15.8Hz), 4.10(1H, br), 4.24(1H, m), 4.90(1H, m),                      5.42(2H, s), 6.63(1H, s), 7.31(1H, dd, J=7.9, 2.0Hz), 7.48                    (1H, t, J=7.9Hz), 7.68(1H, s), 7.85(1H, m), 8.17-8.30(3H,                     m), 12.16(1H, s), 12.50(1H, s), 12.55(1H, br)                            138  (solvent:CDCl.sub.3) 1.18(2H, d, J=6.6Hz), 1.27(3H, t, J=                     7.6Hz), 2.58(3H, s), 2.69(2H, q, J=7.6Hz), 3.72(3H, s), 3.80                  (2H, s), 4.34(4H, m), 4.61(1H, m), 5.37(2H, s), 6.49(1H, s),                  7.06(1H, d, J=7.9Hz), 7.49(1H, s), 7.70(1H, d, J=7.9Hz),                      7.76(1H, t, J=7.9Hz), 7.97(1H, t, J=7.9Hz), 8.25(1H, d, J=                    7.9Hz), 8.29(1H, d, J=7.9Hz), 8.46(1H, brd, J=8.3Hz),                         10.57(1H, s), 12.70(1H, s)                                               139  (solvent:CDCl.sub.3) 1.27(3H, t, J=7.6Hz), 1.41(3H, d, J=                     7.3Hz), 2.59(3H, s), 2.71(2H, q, J=7.6Hz), 3.66(3H, s),                       4.01(2H, ABq, J=29.7Hz, 13.2Hz), 4.51(1H, m), 5.40(2H, s),                    6.50(1H, s), 7.18(1H, dd, J=8.3, 2.0Hz), 7.41(1H, t, J=                       8.3Hz), 7.50(1H, s), 7.75(1H, d, J=7.9Hz), 8.00(1H, t, J=                     7.9Hz), 8.26(1H, d, J=7.9Hz), 8.52(1H, d, J=7.6Hz),                           8.64(1H, dd, J=8.3, 2.0Hz), 12.31(1H, s), 12.63(1H, s)                   140  (solvent:DMSO-d.sub.6) 1.20(3H, t, J=7.6Hz), 1.90-2.52(4H, m),                2.58(3H, s), 2.66(2H, q, J=7.6Hz), 3.70(2H, m),                               3.99(2H, ABq, J=29.7, 16.2Hz), 4.29(1H, m), 5.24(2H, s),                      6.63(1H, s), 7.33(1H, dd, J=7.6, 2.0Hz), 7.47(1H, t, J=                       8.3Hz), 7.68(1H, s), 7.85(1H, dd, J=5.6, 3.3Hz), 8.20(2H, s),                 8.46(1H, dd, J=8.3, 2.0Hz), 12.14(1H, s), 12.51(1H,                      ______________________________________                                             s)                                                                   

                                      TABLE 108                                   __________________________________________________________________________    Ex. No.                                                                            Structural formula                                                       __________________________________________________________________________    141                                                                                 ##STR585##                                                              142                                                                                 ##STR586##                                                              __________________________________________________________________________

                  TABLE 109                                                       ______________________________________                                        .sup.1 H-NMR δ ppm                                                      ______________________________________                                        141  (solvent:CDCl.sub.3) 1.27(3H, t, J=7.6Hz), 1.9-2.3(4H, m),                    2.59(3H, s), 2.71(2H, q, J=7.6Hz), 3.73(3H, s), 3.6-3.9(2H,                   m), 3.87(2H, m), 4.55(1H, m), 5.33(2H, s), 6.47(1H, s),                       7.18(1H, d, J=7.9Hz), 7.51(1H, s), 7.69(1H, d, J=7.9Hz),                      7.74(1H, t, J=7.9Hz), 7.98(1H, t, J=7.9Hz), 8.27(1H, d, J=                    7.9Hz), 8.31(1H, d, J=7.9Hz), 10.34(1H, s), 12.67(1H, s)                 142  (solvent:CDCl.sub.3) 1.27(3H, t, J=7.6Hz), 1.9-2.3(4H, m),                    2.58(3H, s), 2.70(2H, q, J=7.6Hz), 3.74(3H, s), 3.7-3.9(2H,                   m), 3.90(1H, d, J=15.8Hz), 4.26(1H, d, J=15.8Hz), 4.61(1H,                    m), 5.35(2H, s), 6.46(1H, s), 7.25(1H, brd), 7.37(1H, t, J=                   7.9Hz), 7.50(1H, s), 7.73(1H, d, J=7.9Hz), 7.98(1H, t, J=                     7.9Hz), 8.24(1H, d, J=7.9Hz), 8.59(1H, d, J=7.9Hz), 12.29                     (1H, s), 12.65(1H, s)                                                    ______________________________________                                    

                                      TABLE 110                                   __________________________________________________________________________    Ex. No.                                                                             Structural formula                                                      __________________________________________________________________________    143                                                                                  ##STR587##                                                             144                                                                                  ##STR588##                                                             145                                                                                  ##STR589##                                                             146                                                                                  ##STR590##                                                             147                                                                                  ##STR591##                                                             __________________________________________________________________________

                  TABLE 111                                                       ______________________________________                                        .sup.1 H-NMR δ ppm                                                      ______________________________________                                        143  (solvent:CDCl.sub.3) 1.26(3H, t, J=7.4Hz), 1.27(3H, t, J=                     7.4Hz), 1.30(3H, t, J=7.0Hz), 2.58(3H, t), 2.69(2H, q, J=                     7.4Hz), 2.97(1H, dd, J=16.8, 4.6Hz), 3.13(1H, dd, J=16.8,                     4.0Hz), 4.19(2H, qd, J=7.3, 3.0Hz), 4.27(2H, q, J=7.3,                        3.0Hz) 5.06(1H, td, J=8.3, 5.0Hz), 5.27(1H, s), 6.46(1H, s),                  7.49(1H, s), 7.64(1H, dd, J=7.6, 1.0Hz), 7.91(1H, dd, J=7.6,                  7.6Hz), 8.14(1H, dd, J=7.6, 1.0Hz)                                       144  (solvent:CDCl.sub.3) 1.26(3H, t, J=7.6Hz), 1.32(3H, t, J=                     7.3Hz), 2.58(3H, s), 2.68(2H, q, J=7.6Hz), 4.2-4.3(4H, m),                    5.26(2H, s), 6.45(1H, s), 7.49(1H, s), 7.64(1H, d, J=7.6Hz),                  7.92(1H, dd, J=6.9, 7.6Hz), 8.15(1H, d, J=6.9Hz), 12.66                       (1H, s)                                                                  145  (solvent:CDCl.sub.3) 1.25(3H, t, J=7.6Hz), 1.28(3H, t, J=                     7.3Hz), 2.6-2.7(4H, m), 3.7-3.8(2H, m), 4.1-4.2(2H, q, J=                     7.3Hz), 5.24(2H, s), 6.45(1H, s), 7.49(1H, s), 7.61(1H, d, J=                 7.9Hz), 7.90(1H, dd, J=6.6, 7.9Hz), 8.14(1H, d, J=6.6Hz),                     8.42(1H, br), 12.66(1H, s)                                               146  (solvent:CDCl.sub.3) 1.02(6H, dd, J=4.0Hz, 6.9Hz, 1.26(3H, t,                 J=7.6Hz), 2.2-2.4(1H, m), 2.58(3H, s), 2.69(2H, q, J=                         7.6Hz), 3.78(3H, s), 4.75(1H, dd, J=5.3, 9.2Hz), 5.29(2H, s),                 6.49(1H, s), 7.50(1H, s), 7.64(1H, d, J=7.9Hz), 7.91(1H, dd,                  J=7.9, 7.9Hz), 8.15(1H, d, J=7.9Hz), 8.44(1H, d, J=                           9.2Hz), 12.66(1H, s)                                                     147  (solvent:CDCl.sub.3) 1.25(3H, t, J=7.6Hz), 2.58(3H, s),                       2.68(2H, q, J=7.6Hz), 3.85(3H, s),                                            4.0-4.2(2H, m), 4.8-4.9(1H, m), 5.29(2H, s), 6.51(1H, s),                     7.49(1H, s), 7.65(1H, d, J=7.6Hz), 7.92(1H, dd, J=7.6,                        7.9Hz), 8.15(1H, d, J=7.9Hz), 8.80(1H, d, J=7.9Hz), 12.70                     (1H, s)                                                                  ______________________________________                                    

                                      TABLE 112                                   __________________________________________________________________________    Ex. No.                                                                            Structural formula                                                       __________________________________________________________________________    148                                                                                 ##STR592##                                                              149                                                                                 ##STR593##                                                              150                                                                                 ##STR594##                                                              151                                                                                 ##STR595##                                                              152                                                                                 ##STR596##                                                              __________________________________________________________________________

                  TABLE 113                                                       ______________________________________                                        .sup.1 H-NMR δ ppm                                                      ______________________________________                                        148  (solvent:CDCl.sub.3) 1.26(3H, t, J=7.6Hz), 1.32(3H, t, J=                     7.3Hz), 2.0-2.2(1H, m), 2.12(3H, s), 2.3-2.4(1H, m), 2.5-2.7                  (4H, m), 2.58(3H, s), 4.26(2H, q, J=7.3Hz), 4.8-5.0(1H, m),                   5.29(2H, s), 6.47(1H, s), 7.50(1H, s), 7.64(1H, dd, J=1.0,                    7.6Hz), 7.91(1H, dd, J=7.6, 7.6Hz), 8.14(1H, dd, J=1.0Hz,                     7.6Hz), 8.52(1H, d, J=8.6Hz), 12.66(1H, s)                               149  (solvent:CDCl.sub.3) 1.25(3H, t, J=7.6Hz), 2.58(3H, s), 2.67(2H,              q, J=7.6Hz), 3.26(2H, dd, J=1.8Hz, 6.3Hz), 3.75(3H, s),                       5.07(1H, dt, J=8.3, 6.3Hz), 5.22(2H, s), 6.45(1H, s),                         7.1-7.4(5H, m), 7.50(1H, s), 7.62(1H, d, J=7.3Hz),                            7.89(1H, dd, J=6.9Hz, 7.3Hz), 8.11(1H, d, J=6.9Hz),                           8.41(1H, d, J=8.3Hz), 12.67(1H, s)                                       150  (solvent:CDCl.sub.3) 1.25(3H, t, J=7.6Hz), 2.58(3H, s),                       2.68(2H, q, J=7.6Hz), 3.1-3.2(2H, m), 3.76(3H, s), 5.02(1H,                   dt, J=8.6Hz, 5.9Hz), 5.21(2H, d, J=2.0Hz), 6.09(1H, s),                       6.42(1H, s), 6.76(1H, dd, J=2.3Hz, 8.9Hz), 7.02(1H, d, J=                     8.9Hz), 7.50(1H, s), 7.61(1H, d, J=7.6Hz), 7.88(1H, dd, J=                    7.5Hz, 7.6Hz), 8.10(1H, d, J= 7.5Hz), 8.40(1H, d, J=8.6Hz),                   12.63(1H, s)                                                             151  (solvent:CDCl.sub.3) 1.25(3H, t, J=7.6Hz), 2.58(3H, s),                       2.68(2H, q, J=7.6Hz), 3.30(2H, d, J=5.6Hz), 3.79(3H, s),                      5.0-5.1(1H, m), 5.27(2H, d, J=4.6Hz), 6.42(1H, s),                            6.86(1H, d, J=1.3Hz), 7.49(1H, s), 7.6-7.7(2H, m),                            7.89(1H, dd, J=7.6Hz, 7.6Hz), 8.12(1H, dd, J=1.0Hz,                           7.9Hz), 8.8-8.9(1H, m), 12.80(1H, s)                                     152  (solvent:CDCl.sub.3) 1.26(3H, t, J=7.6Hz), 1.57(3H, d, J=                     6.9Hz), 2.58(3H, s), 2.69(2H, q, J=7.6Hz), 3.80(3H, s), 4.82                  (1H, dq, J=6.9Hz, 8.3Hz), 5.28(2H, s), 6.47(1H, s), 7.50(1H,                  s), 7.63(1H, dd, J=1.0Hz, 7.9Hz), 7.91(1H, dd, J=7.9Hz,                       7.9Hz), 8.14(1H, dd, J=1.0, 7.9Hz), 8.43(1H, d, J=8.3Hz),                     12.66(1H, s)                                                             ______________________________________                                    

                                      TABLE 114                                   __________________________________________________________________________    Ex. No.                                                                            Structural formula                                                       __________________________________________________________________________    153                                                                                 ##STR597##                                                              154                                                                                 ##STR598##                                                              155                                                                                 ##STR599##                                                              156                                                                                 ##STR600##                                                              157                                                                                 ##STR601##                                                              __________________________________________________________________________

                  TABLE 115                                                       ______________________________________                                        .sup.1 H-NMR δ ppm                                                      ______________________________________                                        153  (solvent:CDCl.sub.3) 1.26(3H, t, J=7.6Hz), 1.57(3H, d, J=                     7.3Hz), 2.58(3H, s), 2.69(2H, q, J=7.6Hz), 3.80(3H, s), 4.82                  (1H, dq, J=7.3Hz, 7.9Hz), 5.28(2H, s), 6.45(1H, s), 7.50(1H,                  s), 7.63(1H, d, J=7.6Hz), 7.91(1H, dd, J=7.6, 7.6Hz),                         8.14(1H, d, J=7.6Hz), 8.43(1H, d, J=7.9Hz), 12.66(1H, s)                 154  (solvent:CDCl.sub.3) 1.26(3H, t, J=7.6Hz), 2.1-2.5(4H, m),                    2.58(3H, s), 2.69(2H, q, J=7.6Hz), 3.66(3H, s), 3.70(3H, s),                  4.8-4.9(1H, m), 5.29(2H, s), 6.48(1H, s), 7.50(1H, s),                        7.64(1H, dd, J=1.0Hz, 7.6Hz), 7.91(1H, dd, J=7.6Hz,                           7.6Hz), 8.13(1H, dd, J=1.0, 7.6Hz), 8.47(1H, d J=8.6Hz),                      12.65(1H, s)                                                             155  (solvent:CDCl.sub.3) 1.25(3H, t, J=7.3Hz), 1.26(3H, t, J=                     7.6Hz), 2.58(3H, s), 2.69(2H, q, J=7.6Hz), 3.68(2H, d, J=                     1.0Hz), 4.17(2H, q, J=7.3Hz), 4.42(2H, d, J=6.3Hz), 5.26                      (2H, s), 6.45(1H, s), 6.82(1H, t, J=1.0Hz), 7.50(1H, s),                      7.69(1H, d, J=7.9Hz), 7.96(1H, dd, J=7.9Hz, 8.9Hz), 8.63                      (1H, br), 9.80(1H, br), 12.67(1H, s)                                     156  (solvent:CDCl.sub.3) 1.25(3H, t, J=7.6Hz), 2.58(3H, s),                       2.68(2H, q, J=7.6Hz), 2.97(1H, dd, J=6.3Hz, 15.8Hz),                          3.09(1H, dd, J=6.6, 15.8Hz), 3.64(3H, s), 5.27(2H, s), 5.64                   (1H, ddd, J=6.3Hz, 6.6Hz, 8.9Hz), 6.49(1H, s), 7.2-7.5(5H,                    m), 7.49(1H, s), 7.63(1H, d, J=7.3Hz), 7.90(1H, dd, J=                        7.3Hz. 7.3Hz), 8.15(1H, d, J=7.3Hz), 8.80(1H, d, J=8.9Hz),                    12.66(1H, s)                                                             157  (solvent:CDCl.sub.3) 1.25(3H, t, J=7.6Hz), 1.9-2.1(2H, m),                    2.45(2H, t, J=7.6Hz), 2.58(3H, s), 2.68(2H, q, J=7.6Hz),                      3.54(2H, m), 3.68(3H, s), 5.25(2H, s), 6.47(1H, s), 7.50(1H,                  s), 7.61(1H, d, J=7.6Hz), 7.90(1H, dd, J=7.6Hz, 7.9Hz),                       8.10(1H, br), 8.15(1H, d, J=7.9Hz)                                       ______________________________________                                    

                                      TABLE 116                                   __________________________________________________________________________    Ex. No.                                                                            Structural formula                                                       __________________________________________________________________________    158                                                                                 ##STR602##                                                              159                                                                                 ##STR603##                                                              160                                                                                 ##STR604##                                                              161                                                                                 ##STR605##                                                              162                                                                                 ##STR606##                                                              __________________________________________________________________________

                  TABLE 117                                                       ______________________________________                                        .sup.1 H-NMR δ ppm                                                      ______________________________________                                        158  (solvent:CDCl.sub.3) 1.25(3H, t, J=7.6Hz), 1.3-1.5(2H, m),                    1.6-1.8(4H, m), 2.34(2H, t, J=7.6Hz), 2.58(3H, s), 2.68(2H,                   q, J=7.6Hz), 3.4-3.5(2H, m), 3.67(3H, s), 5.25(2H, s),                        6.47(1H, s), 7.49(1H, s), 7.51(1H, d, J=7.9Hz), 7.90(1H,                      dd, J=7.9Hz, 7.9Hz), 8.02(1H, br), 8.16(1H, d, J=7.9Hz),                      12.67(1H, s)                                                             159  (solvent:DMSO-d.sub.6) 1.19(3H, t, J=7.6Hz), 2.52(3H, s), 2.60                (2H, q, J=7.6Hz), 3.5-3.7(2H, m), 4.6-4.8(1H, m), 5.36(2H,                    s), 5.57(1H, d, J=4.3Hz), 6.58(1H, s), 6.6-6.7(1H, m), 6.8-                   6.9(2H, m), 7.1-7.2(1H, m), 7.7-7.8(2H, m), 7.9-8.2(2H, m),                   8.5-8.6(1H, m), 9.34(1H, s), 12.56(1H, s)                                160  (solvent:DMSO-d.sub.6) 1.25(3H, t, J=7.6Hz), 2.59(3H, s), 2.67                (2H, q, J=7.6Hz), 2.73(1H, t, J=5.4Hz), 3.6-3.7(2H, m),                       3.8-3.9(2H, m), 5.25(2H, m), 6.49(1H, s), 7.49(1H, s),                        7.62(1H, d, J=7.6Hz), 7.91(1H, dd, J=7.6Hz, 7.6Hz),                           8.16(1H, d, J=7.6Hz), 8.40(1H, br). 12.69(1H, s)                         161  (solvent:DMSO-d.sub.6) 1.24(3H, t, J=7.6Hz), 2.59(3H, s),                     2.68(2H, q, J=7.6Hz), 3.6-4.0(9H, m), 5.25(2H, s),                            5.84(1H, t, J=4.6Hz), 6.43(1H, s), 7.49(1H, s),                               7.62(1H, d, J=7.6Hz), 7.81(1H, d, J=7.6Hz),                                   7.95(1H, dd, J=7.6Hz, 7.6Hz), 12.62(1H, s)                               162  (solvent:DMSO-d.sub.6) 1.25(3H, t, J=7.6Hz), 1.8-1.9(2H, m),                  2.58(3H, s), 2.67(2H, q, J=7.6Hz), 3.30(1H, t, J=6.4Hz),                      5.25(2H, s), 6.50(1H, s), 7.63(1H, d, J=7.6Hz), 7.91(1H, dd,                  J=7.6Hz, 7.6Hz), 8.16(1H, d, J=7.6Hz), 8.30(1H, br),                          12.71(1H, s)                                                             ______________________________________                                    

                  TABLE 118                                                       ______________________________________                                        Ex.                                                                           No.  Structural formula                                                       ______________________________________                                        163                                                                                 ##STR607##                                                              164                                                                                 ##STR608##                                                              165                                                                                 ##STR609##                                                              166                                                                                 ##STR610##                                                              167                                                                                 ##STR611##                                                              ______________________________________                                    

                  TABLE 119                                                       ______________________________________                                        .sup.1 H-NMR δ ppm                                                      ______________________________________                                        163  (solvent:DMSO-d.sub.6) 1.25(3H, t, J=7.6Hz), 1.32(3H, t, J=                   7.1Hz), 2.57(3H, s), 2.68(2H, q, J=7.6Hz), 3.4-4.0(6H, m),                    5.25(2H, s), 6.45(1H, s), 7.49(1H, s), 7.5-7.9(3H, m), 12.61                  (1H, s)                                                                  164  (solvent:CDCl.sub.3) 1.22(3H, t, J=7.4Hz), 1.32(3H, t, J=                     7.1Hz), 2.57(3H, s), 2.63(2H, q, J=7.4Hz), 4.26(2H, s),                       4.27(2H, q, J=7.1Hz), 5.13(2H, s), 6.44(1H, s), 7.46(1H, s),                  7.49(1H, dd, J=7.6, 7.6Hz), 7.59(1H, d, J=7.6Hz),                             7.77(1H, d, J=7.6Hz), 7.90(1H, s)                                        165  (solvent:CDCl.sub.3) 1.22(3H, t, J=7.4Hz), 1.54(2H, d, J=                     7.0Hz), 2.57(3H, s), 2.63(2H, q, J=7.4Hz), 3.80(3H, s),                       4.82(1H, q, J=7.0Hz), 5.14(2H, s), 6.44(1H, s), 7.46(1H, s),                  7.48(1H, dd, J=7.6, 7.6Hz), 7.58(1H, q, J=7.6 Hz),                            7.76(1H, d, J=7.6Hz), 7.88(1H, s)                                        166  (solvent:CDCl.sub.3) 1.22(3H, t, J=7.6Hz), 1.26(3H, t, J=                     7.1Hz), 1.29(3H, t, J=7.1Hz), 2.57(3H, s), 2.64(2H, q, J=                     7.4Hz), 2.97(1H, dd, J=17.2, 4.3Hz), 3.14(1H, dd, J=17.2,                     4.3Hz), 4.16(2H, q, J=7.1Hz), 4.27(2H, q, J=7.1Hz), 5.04                      (1H, td, J=4.3, 7.9Hz), 5.15(1H, s), 6.45(1H, s), 7.46(1H, s),                7.49(1H, dd, J=7.6, 7.6Hz), 7.59(1H, d J=7.6Hz),                              7.77(1H, d, J=7.6Hz, 7.90(1H, s)                                         167  (solvent:CDCl.sub.3) 1.22(3H, t, J=7.4Hz), 2.57(3H, s),                       2.63(2H, q, J=7.4Hz), 3.83(3H, s), 4.1-4.2(2H, br),                           4.89(1H, dt, J=7.3, 3.6Hz), 5.14(2H, s), 6.44(1H, s), 7.47(1H,                s), 7.49(1H dd, J=7.6, 7.6Hz), 7.60(1H, d, J=7.6Hz),                          7.80(1H, d, J=7.6Hz), 7.91(1H, s)                                        ______________________________________                                    

                  TABLE 120                                                       ______________________________________                                        Ex. No.                                                                              Structural formula                                                     ______________________________________                                        168                                                                                   ##STR612##                                                            169                                                                                   ##STR613##                                                            170                                                                                   ##STR614##                                                            171                                                                                   ##STR615##                                                            172                                                                                   ##STR616##                                                            ______________________________________                                    

                  TABLE 121                                                       ______________________________________                                        .sup.1 H-NMR δ ppm                                                      ______________________________________                                        168  (solvent:CDCl.sub.3) 0.98(3H, t, J=7.3Hz), 1.27(3H, t, J=                     7.3Hz), 1.30(3H, t, J=7.1Hz), 1.5-1.7(2H, m), 2.58(3H, s),                    2.76(2H, t, J=7.6Hz), 2.98(1H, dd, J=16.8, 4.9Hz),                            3.14(1H, dd, J=16.8, 4.9Hz), 4.1-4.4(4H, m), 5.06(1H, dt,                     J=8.6, 4.9Hz), 5.32(2H, s), 6.50(1H, d, J=8.9Hz), 7.61(1H,                    d, J=8.9Hz), 7.66(1H, d, J=8.9Hz), 7.66(1H, d, J=7.9Hz),                      7.91(1H, dd, J=7.6, 7.9Hz), 8.13(1H, d, J=7.6Hz)                         169  (solvent:CDCl.sub.3) 1.02(3H, t, J=7.4Hz), 1.27(3H, t, J=                     7.1Hz), 1.30(3H, t, J=7.1Hz), 1.6-1.7(2H, m), 2.62(3H, t),                    2.74(2H, t, J=7.9Hz), 2.97(1H, dd, J=17.0, 4.9Hz),                            3.13(1H, dd, J=17.0, 4.9Hz), 4.1-4.4(4H, m), 5.06(1H, dt,                     J=8.3, 4.9Hz), 5.29(2H, s), 6.74(1H, d, J=8.8Hz),                             7.57(1H, d, J=8.8Hz), 7.66(1H, d, J=7.9Hz),                                   7.91(1H, dd, J=7.6, 7.9Hz), 8.14(1H, d, J=7.6Hz)                         170  (solvent:CDCl.sub.3) 1.02(3H, t, J=7.3Hz), 1.32(3H, t, J=                     7.3Hz), 1.56(3H, d, J=7.3Hz), 1.6-1.7(2H, m), 2.62(3H, s),                    2.75(2H, t, J=7.9Hz), 3.78(3H, s), 4.26(2H, q, J=7.2Hz),                      4.79(1H, qd, J=7.8, 7.8Hz), 5.29(2H, s), 6.73(1H, d, J=                       7.6Hz), 7.57(1H, d J=8.6Hz), 7.64(1H, d, J=7.9Hz),                            7.91(1H, dd, J=7.6, 7.9Hz), 8.14(1H, d, J=7.6Hz)                         171  (solvent:CDCl.sub.3) 1.24(3H, t, J=7.2Hz), 1.32(3H, t, J=                     7.1Hz), 1.56(3H, d, J=1.0Hz), 2.58(3H, s), 2.69(2H, q, J=                     7.5Hz), 3.88(3H, s), 4.26(2H, q, J=7.2Hz), 4.81(1H, qd, J=                    7.7, 7.7Hz), 5.32(2H, s), 6.51(1H, s), 7.72(1H, s), 7.70(1H, d,               J=8.3Hz), 7.93(1H, dd, J=7.9, 7.6Hz), 8.15(1H, d,                             J=7.9Hz)                                                                 172  (solvent:CDCl.sub.3) 1.24(3H, t, J=7.5Hz), 1.6-2.2(4H, m),                    2.57(3H, s), 2.67(2H, q, J=7.5Hz), 3.5-5.4(7H, m),                            6.44-6.46(2H, m), 7.5-8.0(4H, m)                                         ______________________________________                                    

                                      TABLE 122                                   __________________________________________________________________________    Ex. No.                                                                             Structural formula                                                      __________________________________________________________________________    173                                                                                  ##STR617##                                                             174                                                                                  ##STR618##                                                             175                                                                                  ##STR619##                                                             176                                                                                  ##STR620##                                                             177                                                                                  ##STR621##                                                             __________________________________________________________________________

                  TABLE 123                                                       ______________________________________                                        .sup.1 H-NMR δ ppm                                                      ______________________________________                                        173  (solvent:CDCl.sub.3) 1.25(3H, t, J=7.5Hz), 1.7-2.1(5H, m), 2.57               (3H, s), 2.67(2H, q, J=7.5Hz), 3.0-3.3(2H, m), 3.72(3H, s),                   3.8-4.0(2H, m), 4.5-4.7(2H, m), 5.24(2H, s), 6.44(1H, s),                     7,48(1H, s), 7.53(1H, d, J=7.6Hz), 7.56(1H, d, J=7.6Hz),                      7.84(1H, dd, J=7.9, 7.9Hz)                                               174  (solvent:CDCl.sub.3) 1.25(3H, td, J=7.6, 2.0Hz), 1.5-2.0(4H, m),              2.57(3H, s), 2.68(2H, q, J=7.6Hz), 3.61(1.5H, s), 3.73(1.5H, s),              2.5-5.0(5H, m), 5.24(2H, s), 6.44(1H, s), 7,48(1H, s),                        7.5-8.0(3H, m)                                                           175  (solvent:CDCl.sub.3) 1.26(3H, t, J=7.4Hz), 1.38(2H, d, J=                     6.9Hz), 2.58(3H, s), 2.5-2.7(4H, m), 3.72(3H, s), 4.5-4.6(1H,                 m), 5.27(2H, s), 6.48(1H, s), 7.49(1H, s), 7.61(1H, d, J=                     7.9Hz), 7.89(1H, dd, J=7.9, 7.6Hz), 8.15(1H, d, J=7.6Hz)                 176  (solvent:CDCl.sub.3) 1.22(3H, t, J=6.9Hz), 1.25(3H, t, J=                     7.1Hz), 1.29(3H, t, J=7.1Hz), 2.57(3H, s), 2.68(2H, q, J=                     7.4Hz), 2.78(1H, t, J=7.1Hz), 3.44(1H, q, J=7.1Hz), 3.58                      (1H, q, J=7.1Hz), 3.70(1H, t, J=7.4Hz), 3.79(1H, t, J=                        7.4Hz), 4.10(1H, q, J=7.1Hz), 4.18(1H, q, J=7.1Hz), 5.21                      (1H, s), 5.23(1H, s), 6.43(1H, s), 7.48(1H, s), 7.5-7.9(3H, m),               2.84(1H, t, J=7.1Hz)                                                     177  (solvent:CDCl.sub.3) 1.25(3H, t, J=7.4Hz), 1.29(3H, d, J=                     6.3Hz), 2.58(3H, s), 2.69(2H, q, J=7.4Hz), 4.4-4.6(1H, m),                    4.7-4.9(1H, m), 5.30(2H, s), 6.50(1H, s), 7.50(1H, s), 7.66                   (1H, d, J=7.6Hz), 7.93(1H, dd, J=7.6, 7.6Hz), 8.13(1H, d,                     J=7.6Hz)                                                                 ______________________________________                                    

                  TABLE 124                                                       ______________________________________                                        Ex. No.                                                                              Structural formula                                                     ______________________________________                                        178                                                                                   ##STR622##                                                            ______________________________________                                    

                  TABLE 125                                                       ______________________________________                                        .sup.1 H-NMR δ ppm                                                      ______________________________________                                        178  (solvent:CDCl.sub.3) 1.23(1.2H, t, J=7.6Hz), 1.26(1.8H, t, J=                 7.6Hz), 2.1-2.6(2H, m), 2.59(3H, s), 2.8-3.0(2H, m), 3.8-4.8                  (3H, m), 5.3-5.4(3H, m), 6.44(0.6H, s), 6.48(0.4H, s), 7.5-8.1                (3H, s)                                                                  ______________________________________                                    

                  TABLE 126                                                       ______________________________________                                        .sup.1 H-NMR                 δppm                                       ______________________________________                                        179                                                                                 ##STR623##                                                              180                                                                                 ##STR624##                                                              181                                                                                 ##STR625##                                                              182                                                                                 ##STR626##                                                              183                                                                                 ##STR627##                                                              ______________________________________                                    

                  TABLE 127                                                       ______________________________________                                        .sup.1 H-NMR δ ppm                                                      ______________________________________                                        179  (solvent:CD.sub.3 OD/CDCl.sub.3 (1/4)) 1.26(3H, t, J=7.4Hz), 2.60             (3H, s), 2.70(2H, q, J=7.4Hz), 2.97(1H, dd, J=17.5, 4.8Hz),                   3.15(1H, dd, J=17.5, 4.8Hz), 5.00(1H, t, J=8.9Hz), 5.29(2H,                   s), 6.47(1H, s), 7.53(1H, s), 7.68(1H, d, J=7.9Hz),                           7.95(1H, dd, J=7.9, 7.6Hz), 8.11(1H, d, J=7.6Hz)                         180  (solvent:d.sub.6 -DMSO) 1.18(3H, t, J=7.6Hz), 2.58(3H, S),                    2.62(2H, q, J=7.6Hz), 4.00(2H, d, J=5.9Hz), 5.36(2H, s),                      6.57(1H, s), 7.69(1H, s), 7.73(1H, d, J=6.3Hz),                               8.01(1H, d, J=6.3Hz), 8.10(1H, dd, J=6.3Hz, 6.3Hz),                           8.88(1H, t, J=5.9Hz), 12.55(1H, s)                                       181  (solvent:d.sub.6 -DMSO) 1.18(3H, s, J=7.6Hz), 2.58(3H, s),                    2.61(2H, q, J=7.6Hz), 2.69(2H, q, J=7.6Hz), 3.4-3.5(2H,                       m), 5.35(2H, s), 6.57(1H, s) 7.69(1H, s), 7.70(1H, dd, J=                     1.0Hz, 7.6Hz), 7.99(1H, dd, J=1.0Hz, 7.6Hz), 8.07(1H, dd,                     J=7.6Hz, 7.6Hz), 8.72(1H, t, J=5.9Hz), 12.54(1H, br)                     182  (solvent:d.sub.6 -DMSO) 0.91(6H, t, J=6.4Hz), 1.18(3H, t, J=                  7.6Hz), 2.1-2.2(1H, m), 2.57(3H, s), 2.63(1H, q, J=7.6Hz),                    4.41(1H, dd, J=5.1Hz, 8.9Hz), 5.42(2H, s), 6.63(1H, s),                       7.68(1H, s), 7.76(1H, d, J=6.6Hz), 8.01(1H, d, J=6.9Hz),                      8.11(1H, dd, J=6.6Hz, 6.9Hz), 8.38(1H, d, J=8.9Hz),                           12.55(1H, s)                                                             183  (solvent:d.sub.6 -DMSO) 1.19(3H, t, J=7.6Hz), 2.58(3H, s),                    2.63(2H, q, J=7.6Hz), 3.77(1H, dd, J=3.6Hz, 10,9Hz),                          3.91(1H, dd, J=3.6Hz, 10.9Hz), 4.4-4.5(1H, s), 5.39(2H, s)                    6.61(1H, s), 7.69(1H, s), 7.75(1H, d, J=7.6Hz),                               8.03(1H, dd, J=1.0Hz, 7.6Hz), 8.11(1H, dd, J=7.6Hz,                           7.6Hz), 8.63(1H, d, J=8.3Hz), 12.55(1H, s)                               ______________________________________                                    

                                      TABLE 128                                   __________________________________________________________________________    Ex. No.                                                                            Structural formula                                                       __________________________________________________________________________    184                                                                                 ##STR628##                                                              185                                                                                 ##STR629##                                                              186                                                                                 ##STR630##                                                              187                                                                                 ##STR631##                                                              188                                                                                 ##STR632##                                                              __________________________________________________________________________

                  TABLE 129                                                       ______________________________________                                        .sup.1 H-NMR δ ppm                                                      ______________________________________                                        184  (solvent:d.sub.6 -DMSO) 1.18(3H, t, J=7.6Hz), 2.04(3H, s),                    2.1-2.2(2H, m), 2.4-2.5(2H, m), 2.58(3H, s), 2.62(2H, q, J=                   7.6Hz), 4.5-4.6(1H, m), 5.40(2H, s), 6.60(1H, s), 7.69(1H, s),                7.74(1H, d, J=7.6Hz), 7.99(1H, d, J=6.6Hz),                                   8.09(1H, dd, J=6.6Hz, 7.6Hz), 8.74(1H, d, J=8.2Hz), 12.55                     (1H, s)                                                                  185  (solvent:d.sub.6 -DMSO) 1.16(3H, t, J=7.6Hz), 2.59(3H, s),                    2.63(2H, q, J=7.6Hz), 3.1-3.4(2H, m), 4.6-4.7(1H, m), 5.34                    (2H, s), 6.60(1H, s), 7.1-7.3(5H, m), 7.68(1H, s), 7.71(1H, d,                J=7.6Hz), 7.97(1H, dd, J=1.0Hz, 7.6Hz), 8.07(1H, dd, J=                       7.6Hz, 7.6Hz), 8.61(1H, d, J=8.2Hz), 12.56(1H, s)                        186  (solvent:d.sub.6 -DMSO) 1.17(3H, t, J=7.6Hz), 2.58(3H, s), 2.61               (2H, q, J=7.6Hz), 3.5-3.6(2H, m), 4.6-4.7(1H, m), 5.36(1H,                    s), 6.62(2H, d, J=8.5Hz), 6.99(2H, d, J=8.5Hz), 7.69(1H, s),                  7.73(1H, dd, J=1.0Hz, 7.6Hz), 7.96(1H, dd, J=1.0Hz,                           7.6Hz) 8.08(1H, dd, J=7.6Hz, 7.6Hz), 8.52(1H, d, J=                           8.3Hz), 9.21(1H, br), 12.56(1H, s)                                       187  (solvent:d.sub.6 -DMSO) 1.17(3H, t, J=7.6Hz), 2.58(3H, s),                    2.62(2H, q, J=7.6Hz), 3.20(2H, d, J=6.3Hz), 4.7-4.8(1H,                       m), 5.37(2H, s), 6.60(1H, s), 7.12(1H, s), 7.69(1H, s),                       7.72(1H, d, J=7.6Hz), 7.98(1H, dd, J=0.7Hz, 7.6Hz)                            8.08(1H, dd, J=7.6Hz, 7.6Hz), 8.28(1H, s)                                     8.99(1H, d, J=8.3Hz), 12.54(1H, br),                                     188  (solvent:d.sub.6 -DMSO) 1.89(3H, t, J=7.6Hz), 1.43(3H, d, J=                  7.3Hz), 2.58(3H, s), 2.63(2H, q, J=7.6Hz), 4.4-4.5(1H, m),                    5.39(2H, s), 6.59(1H, s), 7.69(1H, s), 7.73(1H, d, J=7.6Hz),                  8.00(1H, d, J=7.6Hz), 8.09(1H, dd, J=7.6Hz, 7.6Hz),                           8.67(1H, d, J=7.9Hz), 12.55(1H, s)                                       ______________________________________                                    

                                      TABLE 130                                   __________________________________________________________________________    Ex. No.                                                                            Structural formula                                                       __________________________________________________________________________    189                                                                                 ##STR633##                                                              190                                                                                 ##STR634##                                                              191                                                                                 ##STR635##                                                              192                                                                                 ##STR636##                                                              193                                                                                 ##STR637##                                                              __________________________________________________________________________

                  TABLE 131                                                       ______________________________________                                        .sup.1 H-NMR δ ppm                                                      ______________________________________                                        189  (solvent:d.sub.6 -DMSO) 1.89(3H, t, J=7.6Hz), 1.43(3H, d, J=                  7.3Hz), 2.58(3H, s), 2.63(2H, q, J=7.6Hz), 4.4-4.5(1H, m),                    5.39(2H, s), 6.59(1H, s), 7.69(1H, s), 7.73(1H, d, J=7.6Hz),                  8.00(1H, d, J=7.6Hz), 8.09(1H, dd, J=7.6Hz, 7.6Hz),                           8.67(1H, d, J=7.9Hz), 12.55(1H, s)                                       190  (solvent:d.sub.6 -DMSO) 1.86(3H, t, J=7.6Hz), 1.9-2.3(4H, m),                 2.58(3H, s), 2.63(2H, q, J=7.6Hz), 4.4-4.5(1H, m), 5.40(2H,                   s), 6.60(1H, s), 7.69(1H, s), 7.73(1H, d, J=7.6Hz),                           8.00(1H, d, J=7.6Hz), 8.10(1H, dd, J=7.6Hz, 7.6Hz),                           8.70(1H, d, J=8.6Hz), 12.55(1H, s)                                       191  (solvent:d.sub.6 -DMSO) 1.19(3H, t, J=7.6Hz), 2.58(3H, s),                    2.63(2H, q, J=7.6Hz), 3.60(2H, s), 4.24(2H, d, J=5.9Hz),                      5.38(2H, s), 6.58(1H, s), 6.96(1H, s), 7.70(1H, s),                           7.75(1H, d, J=7.6Hz), 8.02(1H, d, J=7.6Hz),                                   8.10(1H, dd, J=7.6Hz, 7.6Hz), 8.98(1H, d, J=5.9Hz),                           12.34(1H, br), 12.55(1H, s)                                              192  (solvent:d.sub.6 -DMSO) 1.17(3H, t, J=7.6Hz), 2.58(3H, s),                    2.62(2H, q, J=7.6Hz), 2.88(1H, dd, J=6.3Hz, 16.2Hz),                          4.0-4.2(1H, m), 5.39(2H, s), 5.4-5.5(1H, m), 6.60(1H, s),                     7.2- 7.7(5H, m), 7.69(1H, s), 7.72(1H, d, J=7.6Hz),                           7.98(1H, d, J=7.3Hz), 8.07(1H, dd, J=7.3Hz, 7.6Hz),                           9.13(1H, d, J=8.9Hz), 12.32(1H, br), 12.56(1H, s)                        193  (solvent:d.sub.6 -DMSO) 1.18(3H, t, J=7.6Hz), 1.7-1.8(2H, m),                 2.26(2H, t, J=7.6Hz), 2.58(3H, s), 2.62(2H, q, J=7.6Hz),                      3.3-3.5(2H, m), 5.36(2H, s), 6.57(1H, s), 7.69(1H, s),                        7.70(1H, d, J=7.6Hz), 7.98(1H, d, J=7.6Hz),                                   8.06(1H, dd, J=7.6Hz, 7.6Hz), 8.68(1H, d, J=5.6Hz), 12.00                     (1H, br), 12.55(1H, br)                                                  ______________________________________                                    

                                      TABLE 132                                   __________________________________________________________________________    Ex. No.                                                                            Structural formula                                                       __________________________________________________________________________    194                                                                                 ##STR638##                                                              195                                                                                 ##STR639##                                                              196                                                                                 ##STR640##                                                              197                                                                                 ##STR641##                                                              198                                                                                 ##STR642##                                                              __________________________________________________________________________

                  TABLE 133                                                       ______________________________________                                        .sup.1 H-NMR δ ppm                                                      ______________________________________                                        194  (solvent:DMSO-d.sub.6) 1.18(3H, t, J=7.6Hz), 1.2-1.3(2H, m),                  1.5-1.7(4H, m), 2.21(2H, t, J=7.3Hz), 2.58(3H, s),                            2.62(2H, q, J=7.6Hz), 5.36(2H, s), 6.57(1H, s),                               7.68(1H, d, J=7.6Hz), 7.69(1H, s), 7.98(1H, d, J=7.6Hz),                      8.06(1H, dd, J=7.6Hz, 7.6Hz), 8.61(1H, m), 12.55(1H, br)                 195  (solvent:CD.sub.3 OD/CDCl.sub.3 (1/4)) 1.21(3H, t, J=7.6Hz), 2.58             (3H, s), 2.64(2H, q, J=7.6Hz), 4.18(2H, d, J=1.7Hz), 5.16                     (2H, s), 6.46(1H, s), 7.49(1H, s), 7.50(1H, dd, J=7.6, 7.6Hz),                7.61(1H, d, J=7.6Hz), 7.81(1H, d, J=7.6Hz), 7.91(1H, s),                 196  (solvent:CD.sub.3 OD:CDCl.sub.3 =1:4) 1.22(3H, t, J=7.4Hz),                   1.55(3H, d, J=6.9Hz), 2.58(3H, s), 2.64(2H, q, J=7.4Hz),                      4.72(1H, td, J=5.9, 7.3Hz), 5.17(2H, s), 6.46(1H, s),                         7.50(1H, dd, J=7.9, 7.6Hz), 7.61(1H, d, J=7.9Hz),                             7.80(1H, d, J=7.6Hz), 7.90(1H, s)                                        197  (solvent:CD.sub.3 OD:CDCl.sub.3 =1:4) 1.22(3H, td, J=7.6, 0.9Hz),             2.65(2H, q, J=7.6Hz), 2.98(1H, dd, J=17.2, 5.0Hz), 3.11                       (1H, dd, J=17.5, 5.0Hz), 4.99(1H, dt, J=4.3, 8.6Hz), 5.18                     (2H, s), 6.47(1H, s), 7.51(1H, dd, J=7.6, 8.3Hz), 7.63(1H, d,                 J=8.3Hz), 7.81(1H, d, J=7.6Hz), 7.92(1H, s), 2.59(3H, s),                     7.51(1H, s)                                                              198  (solvent:CD.sub.3 OD:CDCl.sub.3 =1:4) 1.22(3H, t, J=7.4Hz), 2.58              (3H, s), 2.64(2H, q, J=7.4Hz), 3.97(1H, dd, J=11.6, 3.5Hz),                   4.10(1H, dd, J=11.2, 3.9Hz), 4.67(1H, t, J=3.6Hz), 5.17(1H,                   s), 6.46(1H, s), 7.50(1H, s), 7.51(1H, dd, J=7.6, 7.6Hz),                     7.62(1H, d, J=7.6Hz), 7.85(1H, d, J=7.6Hz)                               ______________________________________                                    

                  TABLE 134                                                       ______________________________________                                        Ex.                                                                           No.  Structural formula                                                       ______________________________________                                        199                                                                                 ##STR643##                                                              200                                                                                 ##STR644##                                                              201                                                                                 ##STR645##                                                              202                                                                                 ##STR646##                                                              203                                                                                 ##STR647##                                                              ______________________________________                                    

                  TABLE 135                                                       ______________________________________                                        .sup.1 H-NMR δ ppm                                                      ______________________________________                                        199  (solvent:CD.sub.3 OD/CDCl.sub.3 (1/4)) 0.99(3H, t, J=7.6Hz), 1.5-             1.7(2H, m), 2.60(3H, s), 2.70(2H, t, J=7.8Hz), 3.0-3.3(2H,                    m), 5.1-5.2(1H, m), 5.27(2H, s), 6.76(2H, d, J=8.9Hz), 7.53                   (2H, d, J=8.9Hz), 7.64(1H, d, J=7.9Hz), 7.90(1H, dd, J=                       7.9, 7.6Hz), 8.11(1H, d, J=7.6Hz)                                        200  (solvent:CD.sub.3 OD/CDCl.sub.3 (1/4)) 0.98(3H, t, J=7.3Hz), 1.5-             1.7(2H, m), 2.57(3H, s), 2.75(2H, t, J=7.6Hz), 3.0-3.3(2H,                    m), 3.75(3H, s), 5.1-5.2(1H, m), 5.31(2H, s), 6.50(1H, d, J=                  8.9Hz), 7.60(1H, d, J=8.9Hz), 7.67(1H, d, J=7.6Hz),                           7.92(1H, dd, J=7.6, 7.3Hz), 8.14(1H, d, J=7.3Hz)                         201  (solvent:CD.sub.3 OD/CDCl.sub.3 (1/4)) 1.01(3H, t, J=7.3Hz),                  1.63(3H, d, J=7.3Hz), 1.5-1.7(2H, m), 2.62(3H, s),                            2.74(2H, t, J=7.6Hz), 3.78(3H, s), 4.80(1H, t, J=7.3Hz),                      5.29(2H, s), 6.73(1H, d, J=8.9Hz), 7.55(1H, d, J=8.9Hz),                      7.66(1H, d, J=7.6Hz), 7.93(1H, dd, J=7.6, 7.6Hz),                             8.15(1H, d, J=7.6Hz)                                                     202  (solvent:CD.sub.3 OD/CDCl.sub.3 (1/4)) 1.23(3H, t, J=7.4Hz),                  1.62(3H, d, J=7.3Hz), 2.58(3H, s), 2.69(2H, q, J=7.4Hz),                      3.87(3H, s), 4.82(1H, q, J=7.3, 7.3Hz), 5.31(2H, s), 6.49(1H,                 s), 7.71(1H, d, J=7.9Hz), 7.71(1H, s), 7.94(1H, dd, J=7.6,                    7.9Hz), 8.16(1H, d, J=7.6Hz)                                             203  (solvent:CD.sub.3 OD/CDCl.sub.3 (1/4)) 1.24(3H, t, J=7.6Hz), 1.7-             2.2(4H, m), 2.57(3H, s), 2.6-2.8(1H, m), 2.67(2H, q, J=                       7.6Hz), 3.0-3.3(2H, m), 3.8-4.0(1H, m), 4.4-4.6(1H, m), 5.25                  (2H, s), 6.44(1H, s), 7.47(1H, s), 7.54(1H, d, J=7.6Hz), 7.57                 (1H, d, J=7.0Hz), 7.85(1H, dd, J=7.6, 7.9Hz)                             ______________________________________                                    

                  TABLE 136                                                       ______________________________________                                        Ex.                                                                           No.  Structural formula                                                       ______________________________________                                        204                                                                                 ##STR648##                                                              205                                                                                 ##STR649##                                                              206                                                                                 ##STR650##                                                              207                                                                                 ##STR651##                                                              208                                                                                 ##STR652##                                                              ______________________________________                                    

                  TABLE 137                                                       ______________________________________                                        .sup.1 H-NMR δ ppm                                                      ______________________________________                                        204  (solvent:CD.sub.3 OD/CDCl.sub.3 (1/4)) 1.25(3H, t, J=7.4Hz), 1.5-             2.3(5H, m), 2.57(3H, s), 2.67(2H, q, J=7.4Hz), 2.7-2.9(1H,                    m), 3.1-4.8(4H, m), 5.25(2H, s), 6.44(1H, s), 7.47(1H, s), 7.5-               7.7(2H, m), 7.85(1H, dd, J=7.6, 7.9Hz)                                   205  (solvent:CD.sub.3 OD/CDCl.sub.3 (1/4)) 1.24(3H, t, J=7.6Hz),                  1.43(3H, d, J=6.6Hz), 2.58(3H, s), 2.67(2H, q, J=7.4Hz),                      2.74(2H, dd, J=5.6, 3.0Hz), 4.5-4.6(1H, m), 5.25(2H, s),                      6.51(1H, s), 7.48(1H, s), 7.61(1H, d, J=7.9Hz),                               7.89(1H, dd, J=7.6, 7.9Hz), 8.14(1H, d, J=7.6Hz)                         206  (solvent:CD.sub.3 OD/CDCl.sub.3 (1/4)) 1.2-1.3(6H, m), 2.57(1H, s),           2.67(2H, q, J=7.5Hz), 2.8-3.0(2H, m), 3.4-3.8(4H, m), 5.24                    (2H, s), 6.4-6.5(1H, m), 7.48(1H, s), 7.5-7.7(2H, m),                         7.85(1H, dd, J=7.6, 7.9Hz),                                              207  (solvent:CD.sub.3 OD/CDCl.sub.3 (1/9)) 1.25(3H, t, J=7.4Hz),                  1.29(3H, d, J=6.3Hz), 2.58(3H, s), 2.69(2H, q, J=7.4Hz),                      4.4-4.6(1H, m), 4.7-4.9(1H, m), 5.30(2H, s), 6.50(1H, s),                     7.50(1H, s), 7.66(1H, d, J=7.6Hz), 7.93(1H, dd, J=7.6,                        7.6Hz), 8.13(1H, d, J=7.6Hz)                                             208  (solvent:CD.sub.3 OD/CDCl.sub.3 (1/9)) 1.23(1.2H, t, J=7.6Hz),                1.26(1.8H, t, J=7.6Hz), 2.1-2.6(2H, m), 2.59(3H, s),                          2.8-3.0(2H, m), 3.8-4.8(3H, m), 5.3-5.4(3H, m), 6.44(0.6H,                    s), 6.48(0.4H, s), 7.5-8.1(3H, s),                                       ______________________________________                                    

                                      TABLE 138                                   __________________________________________________________________________    Ex. No.                                                                            Structural formula                                                       __________________________________________________________________________    209                                                                                 ##STR653##                                                              210                                                                                 ##STR654##                                                              211                                                                                 ##STR655##                                                              212                                                                                 ##STR656##                                                              213                                                                                 ##STR657##                                                              __________________________________________________________________________

                  TABLE 139                                                       ______________________________________                                        .sup.1 H-NMR δ ppm                                                      ______________________________________                                        209  (solvent:CDCl.sub.3 /MeOD(9/1)) 1.26(3H, t, J=7.4Hz), 1.9-                    2.1(1H, m), 2.2-2.4(1H, m), 2.59(3H, s), 2.70(1H, q, J=                       7.4Hz), 3.6-3.9(1H, m), 4.84(1H, dt, J=4.3, 4.6Hz), 5.30(2H,                  s), 6.49(1H, s), 7.53(1H, s), 7.69(1H, d, J=7.6Hz), 7.96(1H,                  dd, J=7.6, 7.6Hz), 8.11(1H, d, J=7.6Hz)                                  210  (solvent:DMSO-d.sub.6) 1.19(3H, t, J=7.6Hz), 2.57(3H, s),                     2.63(2H, q, J=7.6Hz), 3.78(2H, s), 4.02(2H, s), 5.36(2H, s),                  6.56(1H, s), 7.67(1H, s), 7.71(1H, d, J=7.3Hz),                               8.03(1H, dd, J=6.6, 5.9Hz), 8.09(1H, d, J=6.6Hz),                        211  (solvent:CDCl.sub.3 /MeOD(4/1)) 1.26(3H, t, J=7.6Hz),                         1.29(3H, t, J=7.3Hz), 2.59(3H, s), 2.69(2H, q, J=7.5Hz),                      3.68(2H, s), 4.05(2H, s), 4.20(2H, q, J=7.3Hz), 5.29(2H, s),                  6.46(1H, s), 7.52(1H, s), 7.67(1H, d, J=7.9Hz),                               7.95(1H, dd, J=7.6, 7.9Hz), 8.11(1H, d, J=7.6Hz)                         212  (solvent:DMSO-d.sub.6) 1.25(3H, t, J=7.6Hz), 2.58(3H, s),                     2.68(2H, q, J=7.6Hz), 3.50(1H, m), 3.78(1H, m), 4.74(1H,                      m), 5.30(2H, s), 5.46(1H, d, J=2.0Hz), 6.49(1H, s), 6.69(1H,                  m), 6.85(1H, d, J=7.9Hz), 6.91(1H, s), 7.13(1H, t, J=                         7.9Hz), 7.56(1H, s), 7.67(1H, d, J=7.6Hz), 7.98(1H, t, J=                     7.6Hz), 8.08(1H, d, J=7.6Hz), 8.51(1H, m), 9.08(1H, s),                       12.61(1H, s)                                                             213  (solvent:DMSO-d.sub.6) 1.19(3H, t, J=7.6Hz), 2.58(3H, s),                     2.64(2H, q, J=7.6Hz), 3.85(2H, m), 4.55(1H, m), 5.34(1H,                      br), 5.39(2H, s), 6.60(1H, s), 7.68(1H, s), 7.74(1H, d, J=                    7.6Hz), 8.05(1H, t, J=7.6Hz), 8.12(1H, d, J=7.6Hz), 8.63                      (1H, d, J=8.3Hz), 12.55(1H, s), 12.90(1H, br)                            ______________________________________                                    

                                      TABLE 140                                   __________________________________________________________________________    Ex. No.                                                                            Structural formula                                                       __________________________________________________________________________    214                                                                                 ##STR658##                                                              215                                                                                 ##STR659##                                                              216                                                                                 ##STR660##                                                              217                                                                                 ##STR661##                                                              218                                                                                 ##STR662##                                                              __________________________________________________________________________

                  TABLE 141                                                       ______________________________________                                        .sup.1 H-NMR δ ppm                                                      ______________________________________                                        214  (solvent:CDCl.sub.3) 1.25(3H, t, J=7.6Hz), 2.58(3H, s),                       2.68(2H, q, J=7.6Hz), 3.85(3H, s), 4.11(2H, m), 4.88(1H,                      m), 5.29(2H, s), 6.52(1H, s), 7.49(1H, s), 7.65(1H, d, J=                     8.3Hz), 7.91(1H, t, J=8.3Hz), 8.15(1H, d, J=8.3Hz), 8.80                      (1H, d, J=8.3Hz) 12.69(1H, s)                                            215  (solvent:DMSO-d.sub.6) 1.18(3H, t, J=7.3Hz), 2.51(3H, s),                     2.63(2H, q, J=7.3Hz), 3.79(1H, dd, J=11.2Hz, 3.9Hz),                          3.91(1H, dd, J=11.2Hz, 3.9Hz), 4.55(1H, m), 5.48(2H, s),                      6.68(1H, s), 7.70(1H, s), 8.58(1H, d, J=7.9Hz),                               9.05(1H, s), 9.21(1H, s), 12.57(1H, s)                                   216  (solvent:CDCl.sub.3) 1.27(3H, t, J=7.3Hz), 2.59(3H, br),                      2.89(3H, s), 2.68(2H, q, J=7.3Hz), 3.85(3H, s), 4.06(1H, dd,                  J=11.2Hz, 3.6Hz), 4.18(1H, dd, J=11.2Hz, 3.6Hz),                              4.90(1H, m), 5.34(2H, s), 6.52(1H, s), 7.51(1H, s), 8.58(1H,                  m), 9.00(1H, s), 9.37(1H, s), 12.71(1H, s),                              217  (solvent:CDCl.sub.3) 1.27(3H, t, J=7.6Hz), 2.60(3H, s),                       2.71(2H, q, J=7.6Hz), 3.79(2H, s), 3.85-4.10(4H, m),                          4.64-4.80(2H, m), 5.33(2H, s), 6.49(1H, s), 7.57(1H, s),                      7.72(1H, d, J=7.6Hz), 8.00(1H, t, J=7.6Hz), 8.10(1H, d,                       J= 7.6Hz)                                                                218  (solvent:CDCl.sub.3) 1.25(3H, t, J=7.6Hz), 2.57(3H, s),                       2.67(2H, q, J=7.6Hz), 3.2-3.7(2H, m), 3.70(s, 1.2H), 3.81(s,                  1.8H), 4.0-4.3(2H, m), 4.37(0.6H, m), 4.90(0.4H, m), 5.24                     (2H, s), 6.44(1H, s), 7.48(1H, s), 7.5-7.9(3H, m), 12.63(1H,             ______________________________________                                             s)                                                                   

                                      TABLE 142                                   __________________________________________________________________________    Ex. No.                                                                            Structural formula                                                       __________________________________________________________________________    219                                                                                 ##STR663##                                                              220                                                                                 ##STR664##                                                              221                                                                                 ##STR665##                                                              222                                                                                 ##STR666##                                                              223                                                                                 ##STR667##                                                              __________________________________________________________________________

                  TABLE 143                                                       ______________________________________                                        .sup.1 H-NMR δ ppm                                                      ______________________________________                                        219  (solvent:CDCl.sub.3) 1.00(3H, t, J=7.6Hz), 1.24(3H, t, J=                     7.6Hz), 1.81(2H, q, J=7.6Hz), 2.58(3H, s), 2.67(2H, q, J=                     7.6Hz), 3.72(2H, m), 3.94-4.06(4H, m), 5.27(2H, s), 6.56(1H,                  s), 7.48(1H, s), 7.63(1H, d, J=7.6Hz), 7.93(1H, t, J=7.6Hz),                  8.15(1H, d, J=7.6Hz), 8.52(1H, brs), 12.73(1H, s),                       220  (solvent:CDCl.sub.3) 1.24(3H, t, J=7.3Hz), 1.38(3H, s), 2.58(3H,              s), 2.67(2H, q, J=7.3Hz), 3.7-4.1(6H, m), 5.27(2H, s), 6.56                   (1H, s), 7.48(1H, s), 7.64(1H, d, J=7.6Hz), 7.92(1H, t, J=                    7.6Hz), 8.14(1H, d, J=7.6Hz), 8.49(1H, s), 12.73(1H, s)                  221  (solvent:CDCl.sub.3) 1.22(3H, t, J=7.6Hz), 2.57(3H, s),                       2.65(2H, q, J=7.6Hz), 3.83(8H, s), 5.29(2H, s), 6.66(1H, s),                  7.46(1H, s), 7.65(1H, d, J=6.6Hz), 7.93(1H, t, J=7.6Hz),                      8.14(1H, d, J=7.9Hz), 9.12(1H, s), 12.82(1H, s)                          222  (solvent:CDCl.sub.3) 1.26(3H, t, J=7.6Hz), 2.58(3H, s),                       2.67-2.72(2H, m), 3.75-3.82(2H, m), 3.83-3.95(2H, m),                         4.14-4.20(1H, m), 4.20-4.26(2H, m), 5.27(2H, s), 6.45(1H, s),                 7.50(1H, s), 7.62(1H, d, J=6.9Hz), 7.92(1H, t, J=6.9Hz),                      8.13(1H, d, J=6.9Hz), 8.53(1H, d, J=7.9Hz), 12.66(1H, s)                 223  (solvent:DMSO-d.sub.6) 1.21(3H, t, J=7.6Hz), 2.58(3H, s),                     2.65(2H, q, J=7.6Hz), 3.7-3.9(4H, m), 4.61(1H, m), 5.05(1H,                   br), 5.37(2H, s), 6.58(1H, s), 7.65(1H, s), 7.71(1H, dd, J=                   6.8Hz, 2.1Hz), 8.02-8.25(2H, m), 8.39(1H, t, J=5.8Hz), 8.62                   (1H, d, J=8.3Hz), 12.54(1H, s),                                          ______________________________________                                    

                                      TABLE 144                                   __________________________________________________________________________    Ex. No.                                                                            Structural formula                                                       __________________________________________________________________________    224                                                                                 ##STR668##                                                              225                                                                                 ##STR669##                                                              226                                                                                 ##STR670##                                                              __________________________________________________________________________

                  TABLE 145                                                       ______________________________________                                        .sup.1 H-NMR δ ppm                                                      ______________________________________                                        224  (solvent:DMSO-d.sub.6) 1.21(3H, t, J=7.6Hz), 2.57(3H, s),                     2.64(2H, q, J=7.6Hz), 3.54(1H, m), 3.72(1H, m), 4.19(1H,                      m), 5.34(2H, s), 5.59(1H, br), 6.55(1H, s), 7.63(1H, s),                      7.69(1H, dd, J=6.1Hz, 2.8Hz), 8.05(2H, m), 8.51(1H, t, J=                     6.1Hz), 12.55(1H, s), 12.65(1H, br)                                      225  (solvent:CDCl.sub.3) 1.25(3H, t, J=7.6Hz), 1.26(3H, t, J=                     7.3Hz), 2.58(3H, s), 2.68(2H, q, J=7.6Hz), 3.10(1H, dd, J=                    8.9Hz, 5.6Hz), 3.80-3.88(1H, m), 4.06(2H, d, J=5.6Hz), 4.20                   (2H, qJ=7.3Hz), 4.25, 4.35(1H, m), 4.70(1H, m), 5.28(2H,                      s), 6.45(1H, s), 7.15(1H, br), 7.49(1H, s), 7.63(1H, d, J=                    6.9Hz), 7.92(1H, t, J=6.9Hz), 8.15(1H, d, J=6.9Hz), 8.85                      (1H, d, J=7.6Hz), 12.66(1H, s)                                           226  (solvent:CDCl.sub.3) 1.25(3H, t, J=7.6Hz), 2.58(3H, s),                       2.68(2H, q, J=7.6Hz), 3.57(1H, d, J=5.3Hz), 3.83(3H, s),                      3.88(2H, m), 4.44(1H, m), 5.25(2H, s), 6.47(1H, s), 7.49(1H,                  s), 7.63(1H, d, J=7.6Hz), 7.91(1H, t, J=7.6Hz), 8.14(1H, d,                   J=7.6Hz), 8.36(1H, br), 12.68(1H, s)                                     ______________________________________                                    

What is claimed is:
 1. A compound represented by the formula: ##STR671##wherein A is a C₁ -C₅ alkylene chain;B is a pyridinediyl group; R¹ is aC₁ -C₅ alkyl group; R² is a hydroxyl group or a C₁ -C₅ alkoxy group; R³and R⁴ are each independently a hydrogen atom, a C₁ -C₅ alkyl group, aC₂ -C₅ alkenyl group or a C₂ -C₅ alkynyl group; R⁵ is a hydrogen atom, aC₁ -C₅ alkyl group or a hydroxy C₁ -C₅ alkyl group; R⁶ is a CHR²⁰(CH₂)_(n) COOR⁷ group, wherein R⁷ and R²⁰ are each a hydrogen atom and nis 0, 1, 2, 3, 4, or 5;and pharmaceutically acceptable salts thereof. 2.A compound according to claim 1, wherein R¹ is a methyl group and R² isa hydroxyl group.
 3. A compound according to claim 1, wherein R³ is ahydrogen atom and A is a methylene group.
 4. A compound according toclaim 1, wherein R¹ is a methyl group, R² is a hydroxyl group, R³ is ahydrogen atom and A is a methylene group.
 5. A compound according toclaim 4, wherein R⁴ is an ethyl group.
 6. A compound according to claim1, wherein R⁶ is a --CH₂ CH₂ CO₂ H group.
 7. A compound according toclaim 4, wherein R⁶ is a --CH₂ CH₂ CO₂ H group.
 8. A compound accordingto claim 1, which has the formula: ##STR672##
 9. A compound according toclaim 1, which has the formula: ##STR673##
 10. A compound according toclaim 1, which has the formula: ##STR674##
 11. A compound according toclaim 1, which has the formula: ##STR675##
 12. A compound according toclaim 1, which has the formula: ##STR676##
 13. A pharmaceuticalcomposition useful as an antiinflammatory agent or an antiallergicagent, which comprises an effective amount of a compound of claim 1 or apharmaceutically acceptable salt thereof as an active ingredient and apharmaceutically acceptable carrier or diluent.
 14. A method of treatinginflammatory or allergic states which comprises administering apharmaceutically effective amount of a compound of claim 1 or apharmaceutically acceptable salt thereof to a patient.
 15. A compoundaccording to claim 5, wherein R⁶ is a --CH₂ CH₂ CO₂ H group.